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Product Details of [ 26164-26-1 ]

CAS No. :26164-26-1 MDL No. :MFCD00064216
Formula : C9H10O3 Boiling Point : -
Linear Structure Formula :- InChI Key :DIWVBIXQCNRCFE-QMMMGPOBSA-N
M.W : 166.17 Pubchem ID :643325
Synonyms :

Calculated chemistry of [ 26164-26-1 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.22
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 43.88
TPSA : 46.53 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.95 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.42
Log Po/w (XLOGP3) : 0.51
Log Po/w (WLOGP) : 1.13
Log Po/w (MLOGP) : 1.1
Log Po/w (SILICOS-IT) : 1.25
Consensus Log Po/w : 1.08

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.36
Solubility : 7.19 mg/ml ; 0.0433 mol/l
Class : Very soluble
Log S (Ali) : -1.06
Solubility : 14.6 mg/ml ; 0.0876 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.94
Solubility : 1.91 mg/ml ; 0.0115 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.87

Safety of [ 26164-26-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 26164-26-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 26164-26-1 ]

[ 26164-26-1 ] Synthesis Path-Downstream   1~101

  • 1
  • (S)-methyl 2-methoxy-2-phenylacetate [ No CAS ]
  • [ 26164-26-1 ]
YieldReaction ConditionsOperation in experiment
94% With water; lithium hydroxide In tetrahydrofuran; methanol at 20℃; for 2h; 5 General procedure: [0069] As shown in the following Table 5, by using 1 mmol of optically active carboxylic acid esters, each of whichproduced an optically active carboxylic acid, a hydrolysis reaction of a carboxylic acid ester was performed. That is, 1mmol of the carboxylic acid ester and 4 mL of water were added to the ammonium pyrosulfate catalyst (5 mol%) obtainedin Example 1(1), and the mixture was heated at 80°C for 9 to 20 hours while stirring was performed. The reaction mixturethus obtained was diluted with water and was then extracted with ethyl acetate. After organic layers were collected anddried with sodium sulfate, a crude product obtained by condensation under reduced pressure was purified by a columnchromatography, so that an optically active carboxylic acid was obtained. In addition, the optical purity of the reactionproduct was measured by a chiral HPLC. Characteristic chemical shifts (ppm) by 1H NMR (CDCl3) and the analyticalconditions of the chiral HPLC are shown below. In addition, the results are shown in Table 5.
83% With 2C33H37N*H2O7S2; water at 80℃; for 20h; optical yield given as %ee;
With sulfuric acid
395 mg With water; lithium hydroxide In methanol at 20℃; for 2h; 2.2 Step 2. Synthesis of (2S)-2-methoxy-2-phenylacetic acid To a stirred solution of methyl (2S)-2-methoxy-2-phenylacetate (500 mg, 2.77 mmol) in tetrahydrofuran (10.0 mL) was added lithium hydroxide (332 mg, 13.9 mmol) and MeOH: H20 (1:1) (2 ml_:2 mL). The reaction mixture stirred at room temperature for 2 h. Reaction was monitored by TLC and LCMS. After completion of reaction, the solvent was evaporated under reduced pressure and the obtained crude was diluted with ice water and acidified with 5N HCL solution. It was then extracted with ethyl acetate (2 x 50 mL). The organic layer separated, dried over anhydrous Na2SO4 and evaporated under reduced pressure to get compound (2S)-2- methoxy-2-phenylacetic acid (395 mg, 84%) as a white solid. 1HNMR (400 MHz, DMSO-d6): δ 12.90 (s, 1H), 7.32-7.36 (m, 5H), 4.74 (s, 1H), 3.28 (s, 3H).
395 mg With water; lithium hydroxide In methanol at 20℃; for 2h; 2.2 Step 2. Synthesis of (2S)-2-methoxy-2-phenylacetic acid To a stirred solution of methyl (2S)-2-methoxy-2-phenylacetate (500 mg, 2.77 mmol) in tetrahydrofuran (10.0 mL) was added lithium hydroxide (332 mg, 13.9 mmol) and MeOH: H20 (1:1) (2 ml_:2 mL). The reaction mixture stirred at room temperature for 2 h. Reaction was monitored by TLC and LCMS. After completion of reaction, the solvent was evaporated under reduced pressure and the obtained crude was diluted with ice water and acidified with 5N HCL solution. It was then extracted with ethyl acetate (2 x 50 mL). The organic layer separated, dried over anhydrous Na2SO4 and evaporated under reduced pressure to get compound (2S)-2- methoxy-2-phenylacetic acid (395 mg, 84%) as a white solid. 1HNMR (400 MHz, DMSO-d6): δ 12.90 (s, 1H), 7.32-7.36 (m, 5H), 4.74 (s, 1H), 3.28 (s, 3H).

  • 2
  • [ 7021-09-2 ]
  • [ 26164-26-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: LDA / tetrahydrofuran / 0.5 h / 0 °C 1.2: tetrahydrofuran / 2 h / 0 - 20 °C 2.1: (R)-BINOL-SnCl4 / toluene; CH2Cl2 / 1 h / -78 °C 2.2: aq. HCl / toluene; CH2Cl2
Multi-step reaction with 2 steps 1: 38 percent / ClCO2Et, Et3N / tetrahydrofuran 2: aq. HCl / 20 h / Heating
  • 3
  • [ 17199-29-0 ]
  • [ 77-78-1 ]
  • [ 26164-26-1 ]
YieldReaction ConditionsOperation in experiment
37% With sodium hydroxide In water at 45℃; for 3h;
30% With sodium hydroxide In water at 50℃; for 1h;
With sodium hydroxide
With sodium hydroxide In water at 50℃; for 2h;

  • 4
  • [ 496-64-0 ]
  • [ 26164-26-1 ]
  • [ 135382-49-9 ]
  • 5
  • [ 6033-24-5 ]
  • [ 26164-26-1 ]
  • (S)-Methoxy-phenyl-acetic acid (R)-1-methyl-hexyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With dmap; dicyclohexyl-carbodiimide In dichloromethane for 24h;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Inert atmosphere;
  • 6
  • [ 26164-26-1 ]
  • [ 6331-09-5 ]
  • (R)-N-((S)-2-Methoxy-2-phenylacetyl)alanine ethyl ester [ No CAS ]
  • 7
  • [ 26164-26-1 ]
  • [ 66051-01-2 ]
YieldReaction ConditionsOperation in experiment
98.9% With sulfuric acid In diethyl ether; water 7.1 1) 1) Preparation of S-(+)-β-methoxy-2-phenylethanol 3.5 g of S-(+)-α-methoxy-phenylacetic acid (optical purity: 99%, manufactured by Aldrich Co.) was dissolved in 40 ml of diethyl ether. To this solution, 70 ml of a diethyl ether suspension containing 1.05 g of lithium aluminum hydride was gradually dropwise added under stirring and cooling with ice. After completion of the dropwise addition, the mixture was refluxed under heating for one hour and then left to cool to room temperature. Then, 40 ml of 10% sulfuric acid was added under cooling with ice to decompose the excessive reducing agent. The aqueous layer was separated and extracted three times each with 100 ml of diethyl ether. The extracts were combined and washed with 42 ml of 10% sulfuric acid and 100 ml of water. The extract solution thus obtained was dried over anhydrous magnesium sulfate and dried and concentrated under reduced pressure to obtain 31.7 g [[α]D25 +116.1° (C=1.280, ethanol) (yield: 98.9%)] of the above identified compound as colorless oil.
90% With lithium aluminium tetrahydride In diethyl ether for 0.5h; Heating;
82% With borane In tetrahydrofuran at 0 - 20℃;
78% With lithium aluminium tetrahydride In diethyl ether for 2h; Ambient temperature;
56% With lithium aluminium tetrahydride
With lithium aluminium tetrahydride
45 mg With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

  • 8
  • [ 26164-26-1 ]
  • (S)-(+)-O-methylmandeloyl chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With oxalyl dichloride; N,N-dimethyl-formamide In hexane at 20℃; for 24h;
80% With thionyl chloride In benzene for 3h; Ambient temperature;
72% With thionyl chloride for 1h; Ambient temperature;
With oxalyl dichloride In benzene for 14h; Heating;
With oxalyl dichloride In N,N-dimethyl-formamide; acetonitrile at 0℃;
With oxalyl dichloride; N,N-dimethyl-formamide In acetonitrile at 0℃; for 0.166667h;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane; acetonitrile at 0℃; for 0.166667h;
With oxalyl dichloride In N,N-dimethyl-formamide; acetonitrile at 0℃; for 0.0833333h;
With oxalyl dichloride In benzene for 45h; Ambient temperature;
With thionyl chloride at 80℃; for 0.0833333h;
With thionyl chloride for 0.75h; Heating;
With oxalyl dichloride In N,N-dimethyl-formamide; acetonitrile at 0℃; for 0.25h;
With thionyl chloride
With thionyl chloride for 1.5h;
With oxalyl dichloride
With oxalyl dichloride; N,N-dimethyl-formamide In hexane at 20℃; for 48h;
With thionyl chloride at 20℃; for 2h;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃;
With oxalyl dichloride for 2h; Heating;
With oxalyl dichloride for 2h; Ambient temperature;
With thionyl chloride In dichloromethane for 1h; Heating;
With N,N-dimethyl-formamide In hexane at 20℃; for 3h;
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 45℃; for 5h;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 0.5h; Inert atmosphere;
With oxalyl dichloride In hexane at 20℃; for 1h; Inert atmosphere;
With oxalyl dichloride In tetrahydrofuran at 20℃; for 2h; Formation of the MPA Esters To determine the absolute configuration via NMR studies, the (-)-enantiomer of compound II was transformed into the corresponding methoxyphenylacetic (MPA) ester. For the NMR studies both diastereomers of ester 5 were formed from (S) - and (R)-MPA respectively. To this end, MPA (166 mg, 1.0 mmol) was reacted with oxalyl chloride (0.26 mL, 3.0 mmol) in THF (2 mL) in the presence of a catalytic amount of DMF. After stirring for 2 h at ambient temperature, the reaction mixture was concentrated in vacuo. The thus obtained acid chloride of MPA was dissolved in pyridine and a solution of (-)-compound II (30 mg, 0.19 mmol) in pyridine (1 mL) and a catalytic amount of DMAP were added. After stirring for 17 h at ambient temperature, the reaction mixture was quenched with a citric acid solution. The product was extracted with ethyl acetate. The residue obtained after concentration of the combined organic layers was purified by column chromatography. The product was obtained as a white foam (30 mg, 0.099 mmol, 52% yield). The absolute configuration of the (-)-enantiomer was determined to be (1R,3aS,7aR) via NMR studies. Thus, the absolute configuration of the (+)-enantiomer is (1S,3aR,7aS).
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 1h; Cooling with ice;
With thionyl chloride In dichloromethane at 20℃; for 0.5h; 9 (5)-2-methoxy-2-phenylacetyl chloride [20] was separately prepared by stirring (S)-2-methoxy-2-phenylacetic acid and thionylchloride in dry dichloromethane with catalytic amount of dimethylformamide for 30 min. and removing the excess thionylchloride and dichloromethane by under vacuum
With oxalyl dichloride; N,N-dimethyl-formamide In acetonitrile at 0 - 20℃; for 24h; Sealed tube; Di- O-Methyl mandelate ester of 1,4-di[(diethoxy phosphoryl)hydroxymethyl]benzene (2b, 3b) was obtained according to a modified general procedure of Kozlowski.21 Thus oxalyl chloride (1.8 mmol, 0.16mL) was added at 0oC to the reaction medium containing anhydrous acetonitrile (5,4 mL) and DMF (1.8 mmol, 0.19 mL) placed in flask sealed with a rubber septum.The formation of white precipitate was observed, which dissolved after injection of O-(S)-mandelic acid (0,30 g, 1.8 mmol) in 2 mL of acetonitrile. Then the reaction mixture was left for 24 hours at room temperature. After this time volatile components of the reaction mixture were evaporated and the product was redissolved in dry acetonitrile and evaporated to dryness. This procedure was repeated two times to remove remains of unreacted oxalyl chloride. Obtained mandelic chloride was suspended in 2 mL of dry chloroform and compound 1 (0.295 g, 0.72 mmol) dissolved in mixture of dry pyridine (0,3 mL) and dry chloroform (5 mL) was added. The reaction mixture was left at room temperature for 48 hours with stirring and then evaporated. Obtained oil consisted of the mixture of diasteroisomers of compounds 2b and 3b, which were separated and purified by means of silica liquid chromatography using ethyl acetate and propanol (91 v/v) as eluent; ((2b) Rf = 0.5, (3b) Rf = 0.25)
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 0.5h; 9 To a stirred solution of (±)-5,7,3′,4′-tetra-O-benzyl-epicatechin [19] (0.500 g, 0.768 mmol), triethylamine (0.64 ml, 4.61 mmol) and dimethylaminopyridine (0.025 g in 5 ml dry dichloromethane), was added drop wise a freshly prepared solution of (S)-2-methoxy-2-phenylacetyl chloride [20] (0.426 g, 2.31 mmol) in dichloromethane slowly at room temperature under nitrogen. [(S)-2-methoxy-2-phenylacetyl chloride [20] was separately prepared by stirring (S)-2-methoxy-2-phenylacetic acid and thionylchloride in dry dichloromethane with catalytic amount of dimethylformamide for 30 min. and removing the excess thionylchloride and dichloromethane by under vacuum]. After the addition, the reaction mixture was stirred at 40° C. for 5 to 6 hours and monitored by TLC. On complete consumption of the starting material, the reaction mixture was cooled to ambient temperature and the organic layer was washed with water followed by brine solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to yield 0.500 g of a thick viscous semi solid. This viscous solid was treated with methanol (5 ml) to yield solid precipitate. The precipitate was filtered to give [ 21] as a solid (0.235 g) which was enriched in the desired diastereoisomer with a diastereomeric excess of 85% based on HPLC and 1H NMR analysis
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.5h; Schlenk technique; Inert atmosphere;
With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 20℃; for 2h; (3S,5S,7S)- and (3R,5R,7 ?)-tricyclo[2.2.1.02)6]heptane-3,5J7-triyl-tris((S)-2- methoxy-2-phenylacetates), and separation of diastereomers (S)-(+)-2-methoxy-2-phenylacetic acid (MPA) was obtained from mandelic acid and dimethyl sulfate in 37% yield according to the method described by Jones et al. (Jones et al., US 2012/0295329 A1). (S)-(+)-2-methoxy-2-phenylacetic acid (MPA) (12.7 g, 76.5 mmol) was added to a stirred solution of oxalyl chloride (30.0 g, 236.4 mmol) in THF (100 ml_) in the presence of a catalytic amount of DMF at ambient temperature. After stirring for 2 hours the reaction mixture was concentrated in vacuo. The thus obtained acid chloride of MPA was purified by distillation (60 °C/ 7 0"2 mbar), and then was dissolved in ChhCN (100 ml_) and added dropwise to a suspension of nortricycloheptane-3,5,7-triol (2.5 g, 17.6 mmol) 4, pyridine (6.04 g, 76.5 mmol) and a catalytic amount of DMAP in CH3CN. The reaction mixture was stirred for additional 3 hours at ambient temperature, while becoming a clear, reddish solution. Completion of the reaction was checked by TLC. Then the solvent was evaporated in vacuo and the residue was extracted with diethyl ether (3 x 200 ml_). The ethereal solution was concentrated and the obtained oily residue was purified by column chromatography. The tris- mandelates (24% of S,S,S-isomer and 30% of fi. -isomer) were isolated. The mixture of tris-mandelates was separated by careful column chromatography. Analysis: (3S,5S,7S)-Tricyclo[2.2.1.02-6]heptane-3,5,7-triyl-tris((S;-2-methoxy-2- phenylacetate) [a]D20 = -37.0° (CH3OH, 10 mg/mL). M.p. 96-98 °C. RF = 0.4 (cyclohexane : ethyl acetate = 2 : 1). 1H NMR (300 MHz, CDCI3): δ 7.47 - 7.28 (m, 15H), 5. 0 (s, 3H), 4.74 (s, 3H), 3.40 (s, 9H), 2.34 (s, 1 H), 1.53 (s, 3H). 13C NMR (75 MHz, CDCI3): δ 170.32 (s), 135.85 (s), 128.84 (s), 128.72 (s), 127.06 (s), 82.34 (s), 77.53 (s), 57.35 (s), 40.73 (s), 17.89 (s) ESI MS: found 609.2095, calculated (C34H3 NaOg) 609.2101. (3 5R,7R)-tricyclo[2 .1 2'6]heptane-3,5,7-triyl-tris((S)-2-methoxy-2- phenylacetate) [Q]D20 = +116.9° (CHsOH, 10 mg/mL). M.p. 100-103 °C. RF = 0.32 (cyclohexane : ethyl acetate = 2 : 1) 1H NMR (300 MHz, CDCb): δ 7.46 - 7.22 (m, 15H), 4.94 (s, 3H), 4.71 (s, 3H), 3.38 (s, 9H), 1.88 (s, 1 H), 1.85 (s, 3H). 3C NMR (75 MHz, CDCb): δ 170.27 (s), 135.73 (s), 128.86 (s), 128.71 (s), 127.12 (s), 82.24 (s), 77.46 (s), 57.27 (s), 40.27 (s), 18.52 (s). ESI MS: found 609.2097, calculated 609.2101.
With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide for 2h;
With thionyl chloride In dichloromethane at 40℃; for 12h; 12.A Step A: (4aS)-8-Methoxy-3-[(2S)-2-methoxy-2-phenylethanoyl]-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoline; Initially, 36.5 ml of thionyl chloride are added to a solution of 4.94 g of S-methoxyphenylacetic acid in 100 ml of CH2Cl2. The reaction mixture is heated at 40° C. for half a day and is then allowed to cool to ambient temperature. Evaporation to dryness is carried out to obtain an oil. Secondly, the resulting oil in 120 ml of CH2Cl2 is added to a solution of 6.18 g of the compound obtained in Step D of Preparation 1 in 120 ml of CH2Cl2 and 240 ml of 1N NaOH. The whole is stirred vigorously at ambient temperature for 1 hour. The two phases are separated and extraction is carried out once with CH2Cl2. After washing with a saturated NaCl solution and drying over MgSO4, concentration to dryness is carried out. The mixture is purified by flash chromatography over silica gel (petroleum ether/AcOEt 80/20) to yield a mixture of the two diastereoisomers in the form of an oil.The diastereoisomers are then separated by optical preparative liquid chromatography over Chiralpak AD using EtOH as solvent and eluant.

Reference: [1]Pontius, Alexander; Krick, Anja; Kehraus, Stefan; Foegen, Silke E.; Mueller, Michael; Klimo, Karin; Gerhaeuser, Clarissa; Koenig, Gabriele M. [Chemistry - A European Journal, 2008, vol. 14, # 32, p. 9860 - 9863]
[2]Cheung; Field; Hambley; Sternhell [Journal of Organic Chemistry, 1997, vol. 62, # 1, p. 62 - 66]
[3]Trost, Barry M.; Chupak, Louis S.; Luebbers, Thomas [Journal of Organic Chemistry, 1997, vol. 62, # 3, p. 736]
[4]De Gaudenzi, Luigi; Apparao, Satyam; Schmidt, Richard R. [Tetrahedron, 1990, vol. 46, # 1, p. 277 - 290]
[5]Denmark, Scott E.; Senanayake, C. B. W.; Ho, Ginny-Dai [Tetrahedron, 1990, vol. 46, # 13/14, p. 4857 - 4876]
[6]Faunce, James A.; Grisso, Bryan A.; Mackenzie, Peter B. [Journal of the American Chemical Society, 1991, vol. 113, # 9, p. 3418 - 3426]
[7]Singh; Reamer; Zink; Schmatz; Dombrowski; Goetz [Journal of Organic Chemistry, 1991, vol. 56, # 19, p. 5618 - 5622]
[8]Trost, Barry M.; Belletire, John L.; Godleski, Stephen; McDougal, Patrick G.; Balkovec, James M.; et al. [Journal of Organic Chemistry, 1986, vol. 51, # 12, p. 2370 - 2374]
[9]Sucrow, Wolfgang; Brinkkoetter, Gustav [Chemische Berichte, 1985, vol. 118, # 11, p. 4330 - 4340]
[10]Katz, Thomas J.; Sudhakar, Anantha; Teasley, Mark F.; Gilbert, Adam M.; Geiger, William E.; Robben, Matthew P.; Wuensch, Martin; Ward, Michael D. [Journal of the American Chemical Society, 1993, vol. 115, # 8, p. 3182 - 3198]
[11]Smith, Amos B.; Wood, John L.; Keenan, Terence P.; Liverton, Nigel; Visnick, Melean [Journal of Organic Chemistry, 1994, vol. 59, # 22, p. 6652 - 6666]
[12]Denmark, Scott E.; Middleton, Donald S. [Journal of Organic Chemistry, 1998, vol. 63, # 5, p. 1604 - 1618]
[13]Roos, Gregory H.P.; Raab, Conrad E.; Emslie, Neville D.; Doyle, Michael P.; Lynch, Vincent [Australian Journal of Chemistry, 1998, vol. 51, # 1, p. 1 - 8]
[14]Yatabe, Takumi; Kayakiri, Hiroshi; Kawai, Yoshio; Oku, Teruo; Tanaka, Hirokazu [Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 10, p. 1556 - 1565]
[15]Luzzio, Frederick A.; Duveau, Damien Y. [Tetrahedron Asymmetry, 2002, vol. 13, # 11, p. 1173 - 1180]
[16]Abad, José-Luis; Camps, Francisco [Tetrahedron, 2004, vol. 60, # 50, p. 11519 - 11525]
[17]Silva, Franck; Sawicki, Marcin; Gouverneur, Veronique [Organic Letters, 2006, vol. 8, # 23, p. 5417 - 5419]
[18]Fancelli, Daniele; Moll, Jürgen; Varasi, Mario; Bravo, Rodrigo; Artico, Roberta; Berta, Daniela; Bindi, Simona; Cameron, Alexander; Candiani, Ilaria; Cappella, Paolo; Carpinelli, Patrizia; Croci, Walter; Forte, Barbara; Giorgini, Maria Laura; Klapwijk, Jan; Marsiglio, Aurelio; Pesenti, Enrico; Rocchetti, Maurizio; Roletto, Fulvia; Severino, Dino; Soncini, Chiara; Storici, Paola; Tonani, Roberto; Zugnoni, Paola; Vianello, Paola [Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7247 - 7251]
[19]Roy, Bernard L.; Deslongchamps, Pierre [Canadian Journal of Chemistry, 1985, vol. 63, p. 651 - 654]
[20]Fornasier, Roberto; Reniero, Fabiano; Scrimin, Paolo; Tonellato, Umberto [Journal of the Chemical Society. Perkin transactions II, 1987, p. 193 - 196]
[21]Van Vliet, L. Alexander; Rodenhuis, Nienke; Dijkstra, Durk; Wikström, Håkan; Pugsley, Thomas A.; Serpa, Kevin A.; Meltzer, Leonard T.; Heffner, Thomas G.; Wise, Lawrence D.; Lajiness, Mary E.; Huff, Rita M.; Svensson, Kjell; Sundell, Staffan; Lundmark, Max [Journal of Medicinal Chemistry, 2000, vol. 43, # 15, p. 2871 - 2882]
[22]Location in patent: experimental part Affeld, Sven; Kehraus, Stefan; Waegele, Heike; Koenig, Gabriele M. [Journal of Natural Products, 2009, vol. 72, # 2, p. 298 - 300]
[23]Shi, Jianyou; Xu, Guobin; Zhu, Wei; Ye, Haoyu; Yang, Shengyong; Luo, Youfu; Han, Jing; Yang, Jincheng; Li, Rui; Wei, Yuquan; Chen, Lijuan [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 14, p. 4273 - 4278]
[24]Kuwano, Ryoichi; Kameyama, Nao; Ikeda, Ryuhei [Journal of the American Chemical Society, 2011, vol. 133, # 19, p. 7312 - 7315]
[25]Hou, Xian-Feng; Yao, Sheng; Mandi, Attila; Kurtan, Tibor; Tang, Chun-Ping; Ke, Chang-Qiang; Li, Xi-Qiang; Ye, Yang [Organic Letters, 2012, vol. 14, # 2, p. 460 - 463]
[26]Current Patent Assignee: UNIVERSITY OF GRONINGEN - US2012/58977, 2012, A1 Location in patent: Page/Page column 8
[27]Location in patent: experimental part Dai, Yumin; Harinantenaina, Liva; Brodie, Peggy J.; Callmander, Martin W.; Randrianaivo, Richard; Rakotonandrasana, Stephan; Rakotobe, Etienne; Rasamison, Vincent E.; Shen, Yongchun; Tendyke, Karen; Suh, Edward M.; Kingston, David G. I. [Journal of Natural Products, 2012, vol. 75, # 3, p. 479 - 483]
[28]Current Patent Assignee: EPIRIUM BIO - WO2012/101652, 2012, A2 Location in patent: Page/Page column 36
[29]Malinowska, Barbara; Mlynarz, Piotr; Lejczak, Barbara [ARKIVOC, 2012, vol. 2012, # 4, p. 299 - 313]
[30]Current Patent Assignee: EPIRIUM BIO - US2014/31421, 2014, A1 Location in patent: Paragraph 0179
[31]Qi, Shuai; Kang, Chuan-Qing; Han, Fu-She [Magnetic Resonance in Chemistry, 2015, vol. 53, # 3, p. 181 - 187]
[32]Ikeda, Ryuhei; Kuwano, Ryoichi [Chemistry - A European Journal, 2016, vol. 22, # 25, p. 8610 - 8618]
[33]Current Patent Assignee: MERCK KGAA - WO2016/198143, 2016, A1 Location in patent: Page/Page column 32-34
[34]Kozel, Volodymyr; Daniliuc, Constantin-Gabriel; Kirsch, Peer; Haufe, Günter [Angewandte Chemie - International Edition, 2017, vol. 56, # 48, p. 15456 - 15460][Angew. Chem., 2017, vol. 129, p. 15659 - 15663,5]
[35]Current Patent Assignee: SERVIER MONDE - US2008/188460, 2008, A1 Location in patent: Page/Page column 8-9
  • 9
  • [ 1565-80-6 ]
  • [ 26164-26-1 ]
  • (S)-(-)-2-methylbutyl (S)-(+)-2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4h; Preparation of model MPA esters A mixture of 2 mL of S-2-methylbutanol, 5.7 mg of S-MPA, 9.4 mg of DCC, and catalytic amount of DMAP in 300 mL of CH2Cl2 was allowed to stand at room temperature for 4 h. The product was directly applied for separation on preparative silica TLC (EtOAc) to give 5.1 mg of S-MPA ester. R-MPA ester was prepared in a similar way.
  • 10
  • [ 26164-26-1 ]
  • [ 188907-62-2 ]
  • (3'S,4'R)-4'-(6-chloropurin-9-yl)-1'-methoxycarbonyl-3'-((S)-α-methoxyphenylacetyloxy)-cyclopent-1'-ene [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h;
  • 11
  • [ 26164-26-1 ]
  • [ 181075-66-1 ]
  • (S)-3-((S)-2-Methoxy-2-phenyl-acetylamino)-5-methyl-hexanoic acid methyl ester [ No CAS ]
  • 12
  • [ 26164-26-1 ]
  • [ 729593-92-4 ]
  • (-)-(2S)-[(2S,3R,4R,5S)-2-phenyl-3-(p-tolylsulfonyl)-3,4-epoxytetrahydro-2H-pyran-3-yl] 2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 3h;
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 3h;
  • 13
  • [ 26164-26-1 ]
  • [ 794513-82-9 ]
  • (S)-Methoxy-phenyl-acetic acid (1S,4S)-1-allyl-5-(tert-butyl-diphenyl-silanyloxy)-4-methyl-3-methylene-pentyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.333333h;
95% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;
  • 14
  • [ 19132-06-0 ]
  • [ 26164-26-1 ]
  • (2S,3S)-2,3-butananediol bis[(S)-α-methoxy-α-phenylacetic acid ester] [ No CAS ]
  • 15
  • [ 26164-26-1 ]
  • [ 72345-23-4 ]
  • (S)-Methoxy-phenyl-acetic acid (1S,3S)-3-((S)-2-methoxy-2-phenyl-acetoxy)-1-methyl-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 2h;
  • 16
  • [ 342906-79-0 ]
  • [ 26164-26-1 ]
  • (3E,2R)-1,1-bis[((S)-methoxyphenylacetoxy)methyl]-1-benzyl-4-phenyl-4-penten-3-yl (S)-methoxyphenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% Stage #1: (S)-2-methoxy-2-phenylacetic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane for 0.0833333h; Stage #2: (4E,3R)-2-hydroxymethyl-2-benzyl-5-phenyl-4-pentene-1,3-diol In dichloromethane at 20℃; for 1h; Further stages.;
  • 17
  • [ 26164-26-1 ]
  • [ 872884-44-1 ]
  • (S)-Methoxy-phenyl-acetic acid 1-cyclohexyl-2-methyl-pent-4-enyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h;
  • 18
  • [ 57090-45-6 ]
  • [ 26164-26-1 ]
  • (R)-3-chloropropane-1,2-diol bis-(S)-α-methoxyphenylacetic acid ester [ No CAS ]
  • 19
  • [ 26164-26-1 ]
  • [ 174810-05-0 ]
  • (S)-2-phthalimido-3-butenyl (S)-O-methylmandelate [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 12h;
  • 20
  • [ 307972-77-6 ]
  • [ 26164-26-1 ]
  • (2S,3S,5S,6S)-3-((S)-2-Methoxy-2-phenyl-acetoxy)-5-methyl-6-phenyl-tetrahydro-pyran-2-carboxylic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h;
  • 21
  • [ 953814-57-8 ]
  • [ 26164-26-1 ]
  • (S,S)-methoxyphenylacetic acid 1,8,8-trimethyl-3-triisopropylsilanyloxymethyl-deca-3,6-dien-19-ynyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h;
  • 22
  • [ 20407-74-3 ]
  • [ 26164-26-1 ]
  • (S)-MPA thioester of (S)-butane-2-thiol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Inert atmosphere;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; Inert atmosphere; 1 4.1. General procedures General procedure: The thioesters (4-7 and 11-13) were prepared by treatment of the thiol (1 equiv; 0.150 mmol) with the corresponding arylmethoxyacetic acid or aryl-tert-butoxyacetic acid (1.2 equiv; 0.180 mmol) in the presence of EDCHCl (1.2 equiv; 0.180 mmol) and DMAP (catalytic) in dry CH2Cl2 (2.5 mL), and under argon atmosphere (EDCHCl=1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, DMAP=4-dimethylaminopyridine). The mixtures were stirred at room temperature for 2-4 h approximately. The organic layers were washed with water, HCl (1 M), water, NaHCO3 (sat) and water, then dried (anhydrous Na2SO4) and concentrated under reduced pressure to obtain the thioesters. Final purifications were achieved by flash column chromatography on silica gel 230-400 mesh (elution with hexane/ethyl acetate mixtures). Yields ranging from 80 to 95 %.
  • 23
  • [ 26164-26-1 ]
  • [ 50764-49-3 ]
  • (S)-MPA thioester of (S)-octane-2-thiol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Inert atmosphere;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; Inert atmosphere; 1 4.1. General procedures General procedure: The thioesters (4-7 and 11-13) were prepared by treatment of the thiol (1 equiv; 0.150 mmol) with the corresponding arylmethoxyacetic acid or aryl-tert-butoxyacetic acid (1.2 equiv; 0.180 mmol) in the presence of EDCHCl (1.2 equiv; 0.180 mmol) and DMAP (catalytic) in dry CH2Cl2 (2.5 mL), and under argon atmosphere (EDCHCl=1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, DMAP=4-dimethylaminopyridine). The mixtures were stirred at room temperature for 2-4 h approximately. The organic layers were washed with water, HCl (1 M), water, NaHCO3 (sat) and water, then dried (anhydrous Na2SO4) and concentrated under reduced pressure to obtain the thioesters. Final purifications were achieved by flash column chromatography on silica gel 230-400 mesh (elution with hexane/ethyl acetate mixtures). Yields ranging from 80 to 95 %.
  • 24
  • [ 26164-26-1 ]
  • [ 53273-24-8 ]
  • (S)-MPA thioester of (+)-neomenthanethiol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Inert atmosphere;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; Inert atmosphere; 1 4.1. General procedures General procedure: The thioesters (4-7 and 11-13) were prepared by treatment of the thiol (1 equiv; 0.150 mmol) with the corresponding arylmethoxyacetic acid or aryl-tert-butoxyacetic acid (1.2 equiv; 0.180 mmol) in the presence of EDCHCl (1.2 equiv; 0.180 mmol) and DMAP (catalytic) in dry CH2Cl2 (2.5 mL), and under argon atmosphere (EDCHCl=1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, DMAP=4-dimethylaminopyridine). The mixtures were stirred at room temperature for 2-4 h approximately. The organic layers were washed with water, HCl (1 M), water, NaHCO3 (sat) and water, then dried (anhydrous Na2SO4) and concentrated under reduced pressure to obtain the thioesters. Final purifications were achieved by flash column chromatography on silica gel 230-400 mesh (elution with hexane/ethyl acetate mixtures). Yields ranging from 80 to 95 %.
  • 25
  • [ 26164-26-1 ]
  • [ 100-51-6 ]
  • benzyl α-methoxyphenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With molecualar sevies 4A In toluene at 120℃; for 13h; 3.14 Example 3 [Scope of Substrate Application] By combining diversely the carboxylic acid of various structure and alcohol, the scope of substrate application of the tetravalent hafnium compound was examined. A Soxhlet tube filled with dried molecular sieves 4A (about 1.5 g) was connected to the top of a 5 ml eggplant flask contained with a teflon coated magnetic stirrer, and a cooling tube was further attached over said Soxhlet tube. Unless there is a particular point of concern, toluene solvent (2 ml) and 0.1 mol %, 0.2 mol % or 1 mol % of hafnium chloride (IV)•(THF)2 were added to carboxylic acid (10 mmol) and alcohol (10 mmol), and heating reflux was conducted in the argon for several hours at 120°C. After the reaction, the mixture solution was purified by direct silica gel column chromatography (eluant hexane:ethyl acetate=4:1 to 8:1), and the solution was dried under reduced pressure. The results are shown in Table 2. In Table 2, the following are shown: for the experiment of Entry 3, toluene solvent (5 ml) was used; for the experiment of Entry 4, 4-phenyl butanoic acid (36 mmol) and toluene solvent (4 ml) were used; for the experiment of Entry 5, the numerical value of yield showed in parenthesis is the value in the case the inventors wanted to use the catalyst; for the experiment of Entry 9, o-xylene solvent (2 ml) was used; for the experiment of Entry 14, enantiomer of carboxylic acid was used and at a yield of 84%, the enantiomer of ester was obtained; for the experiment of Entry of 17, 1,3,5-mesitylene solvent(2 ml) was used; for the experiments of Entry 18 and 19, the lactone value is shown for the yield. [TABLE-US-00002] TABLE 2 [CHEMMOL-00003] HfCl4.(THF)2 reaction entryRCO2H ROH (1 mol %) time (h) yield (%) 1 [CHEMMOL-00004] [CHEMMOL-00005] 0.2 6 97 2 [CHEMMOL-00006] [CHEMMOL-00007] 0.2 24 92 3 [CHEMMOL-00008] [CHEMMOL-00009] 0.1 18 >99 4 [CHEMMOL-00010] EtC(CH2OH)3 0.2 24 >99 5 [CHEMMOL-00011] [CHEMMOL-00012] 0.2 5 94 (36) 6 [CHEMMOL-00013] l-menthol 0.2 36 >99 7 [CHEMMOL-00014] [CHEMMOL-00015] 0.2 13 >99 8 [CHEMMOL-00016] Et3COH 1.0 24 0 9 [CHEMMOL-00017] PhOH 0.2 36 91 10 [CHEMMOL-00018] [CHEMMOL-00019] 0.2 10 92 11 [CHEMMOL-00020] [CHEMMOL-00021] 0.1 18 98 12 [CHEMMOL-00022] [CHEMMOL-00023] 0.2 7 96 13Et2CHCO2H [CHEMMOL-00024] 0.2 60 98 14 [CHEMMOL-00025] [CHEMMOL-00026] 0.2 13 98 15PhCO2H [CHEMMOL-00027] 0.2 15 92 16 [CHEMMOL-00028] [CHEMMOL-00029] 0.2 10 92 17PhCO2H3,5-Me2C5H3OH 1.0 24 95 18 [CHEMMOL-00030] 0.2 10 98 19 [CHEMMOL-00031] 0.2 10 94 [0022] As it is also shown in Table 2, every carboxylic acid reacted with primary and secondary alcohol, under the presence of the catalyst of 0.2 mol % and under, and produced ester quantitatively, but as it is shown from the experiment of Entry 8, it did not react with tertiary alcohol. Furthermore, as it is shown from the experiment of Entry 17, the aromatic substrates (benzoic acid and phenol) showed lower reactivity compared to aliphatic substrates, and when carboxylic acid and alcohol are both aromatics, the ester could be obtained at a high yield, by increasing the catalyst amount up to 1 mol %. Moreover, when the reactivity is low, it is also effective to use a benzene solvent of higher boiling point, for example, o-xylene of the experiment of Entry 9 or 1,3,5-mesitylene of the experiment of Entry 17 and to conduct heating reflux.
  • 26
  • [ 7021-09-2 ]
  • [ 3966-32-3 ]
  • [ 26164-26-1 ]
YieldReaction ConditionsOperation in experiment
With CSP 9803/5601; trifluoroacetic acid In di-isopropyl ether Resolution of racemate; 17 The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor α, are indicated.
With CSP 9803/5301; trifluoroacetic acid In di-isopropyl ether Resolution of racemate; 17 The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor α, are indicated.
With CSP 9803/5901; trifluoroacetic acid In di-isopropyl ether Resolution of racemate; 17 The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor α, are indicated.
With CSP 9803/5701; trifluoroacetic acid In di-isopropyl ether Resolution of racemate; 17 The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor α, are indicated.
With CSP 9803/5801; trifluoroacetic acid In di-isopropyl ether Resolution of racemate; 17 The various columns containing the CSPs are conditioned with the eluant used, for 1 hour, before injection of the racemic product to be separated. [0102] The chromatographic conditions are as follows: [0103] mobile phase flow rate: 1 ml/mn; [0104] UV detection at 254 nm; [0105] optical density scale: 0.1; [0106] injection of a solution comprising 1 mg of the racemic product to be separated given below in 1 ml of eluant also given below. The results of the rounds of chromatography are given in tables 1 and 2 below. [0108] For each measurement, the retention times t of each of the recovered enantiomers, and also the capacity factor k'2 and the selectivity factor α, are indicated.
With (3R,4S)-4-(3,5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthren-3-yl covalently linked to 3-propyl silica surface In hexane; acetic acid; isopropyl alcohol at 25℃; Resolution of racemate;
With cellulose-modified silica gel In hexane; isopropyl alcohol Resolution of racemate;
With ammonium acetate; acetic acid In ethanol; water Resolution of racemate;

  • 27
  • [ 26164-26-1 ]
  • [ 844868-72-0 ]
  • [ 844868-73-1 ]
YieldReaction ConditionsOperation in experiment
60% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1h; 1.g To a solution of diol 21 (33 mg, 0.1 mmol), EDC (19 mg, 0.1 mmol), and DMAP (4 mg, 0.03 lamol), in CH2C12 (2 mL) was added S- (+)-O-methyl mandelic acid (12 mg, 0.1 mmol). After 1 hour at rt, water was added and the resulting solution was extracted with CH2C12. The combined organic phase was dried (MgS04) and concentrated. Further purification by flash chromatography (5: 1 to 2: 1 hexanes: ethyl acetate) afforded the mandelate ester 22 (25 mg, 60%) as a clear oil, along with a small amount of the diastereomeric ester (not isolated): [a] 264D = +42. 1 (c 0.28, CHCl3); 1H NMR (CDCl3) No. 7.46 (dd, J= 7.9, 1.8 Hz, 2H), 7.40-7. 32 (m, 3H), 6.72 (s, 1H), 6. 64- (s, 1H), 5.27 (t, J= 8. 0 Hz, 1H), 4.79 (s, 1H), 4.65 (s, 2H), 3.77 (s, 3H), 3.43 (s, 3H), 3. 33 (d, J= 7.9 Hz, 2H), 1.96 (t, J= 8.0 Hz, 2H), 1.78-1. 61 (m, 3H), 1.64 (s, 3H), 1.00 (s, 9H), 0.94 (s, 15H), 0.18 (s, 6H), 0.09 (s, 6H) ;"C NMR 8 170.4, 149.7, 141. 3,136. 5,135. 0, 133.7, 132.1, 129.0, 128.7 (2C), 127.2 (2C), 123.1, 119.0, 1 07. 3,82. 6,80. 7,72. 3, 65.0, 57. 3, 54.7, 35. 0,28. 5,28. 1,26. 1 (3C), 26.0 (3C), 25. 9, 24.6, 18.9, 18.4, 16.3,- 3.9 (2C), -5.1 (2C); HRMS (ESI) calcd for C39H6407Si2Na (M+Na) + 723.4088, found 723.4090.
  • 28
  • C40H49N5O7S*2ClH [ No CAS ]
  • [ 26164-26-1 ]
  • C49H57N5O9S [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 20℃; for 3h; D.119.7 To a solution mixture of the product from step 6 of Example 119 (0.062 g, 0.076 mmol) DIEA (0.040 g, 0.31 mmol) and S-(+)-α-methoxy phenylacetic acid (0.019 g, 0.095 mmol) in DCM (2 mL) was added HATU (0.044 g, 0.114 mmol). After stirring at rt for 3 h, the reaction was diluted with DCM (5 mL) washed with 5% aqueous NaHCO3 (3 mL). Th aqueous layer was extracted with DCM (5 mL). The combined organic layer was washed with 5% aqueous citric acid (3 mL), dried over MgSO4 and concentrated. The resulting brown viscous oil was purified by flash column chromatography (SiO2, 95:5 DCM:MeOH) to give as a light brown solid (0.051 g, 75% yield): 1H NMR (500 MHz, CD3OD) δ 0.08-0.12 (m, 3H) 0.46-0.50 (m, 2H) 0.70-0.74 (m, 1 H) 0.94 (dd, J=8.85, 4.27 Hz, 1 H) 0.96-0.98 (m, 2H) 1.01 (s, 9H) 1.04 (s, 2H) 1.12-1.14 (m, 1 H) 1.15-1.17 (m, 1 H) 1.23-1.27 (m, 1 H) 1.44 (dd, J=9.46, 5.49 Hz, 1 H) 1.49-1.53 (m, 1 H) 1.61 (m, 1 H) 1.81 (dd, J=14.80, 7.17 Hz, 1 H) 1.85 (dd, J=7.93, 2.44 Hz, 1 H) 1.89 (dd, J=13.73, 6.71 Hz, 1 H) 1.93 (dd, J=13.50, 6.77 Hz, 1 H) 2.23 (q, J=8.95 Hz, 1 H) 2.33-2.37 (m, 1 H) 2.66-2.70 (m, 1H) 3.25 (s, 3H) 3.25-3.29 (m, 2H) 3.33-3.37 (m, 2H) 3.98 (s, 3H) 4.13 (dd, J=12.05, 3.51 Hz, 1 H) 4.37 (s, 1 H) 4.57 (d, J=10.68 Hz, 1 H) 4.59 (d, J=9.77 Hz, 1 H) 5.12 (dd, J=10.38, 1.53 Hz, 1 H) 5.29 (dd, J=17.24, 1.37 Hz, 1 H) 5.61 (s, 1 H) 5.72-5.76 (m, 1 H) 7.30 (d, J=9.77 Hz, 3H) 7.32 (d, J=1.83 Hz, 2H) 7.45 (d, J=2.44 Hz, 1 H) 7.84 (d, J=9.46 Hz, 1 H) 8.03 (d, J=9.16 Hz, 1 H) 8.06 (s, 1 H) 8.07 (d, J=1.53 Hz, 1 H), MS m/z 892 (MH+).
  • 29
  • [ 166180-82-1 ]
  • [ 26164-26-1 ]
  • (RS)-ethyl 2-[N-(2-methoxy-2-phenylacetamido)]-3-[3-hydroxy-5-(2-thienyl)isoxazol-4-yl]propionate [ No CAS ]
  • (S)-(+)-O-methylmandeloyl chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With triethanolamine In dichloromethane 15 (-)-2-Amino-3-[3-hydroxy-5-(2-thienyl)isoxazol-4-yl]propionic Acid, 15a. A solution of (R S)-2-amino-3-[3-ethoxy-5-(2-thienyl)isoxazol-4-yl]propionic acid (24.9 g; 78.1 mmol) in CH2Cl2(1200 mL) and TEA (45 mL) was heated to reflux temperature. (S)-(+)-2-methoxy-2-phenylacetyl chloride (16.2 g; 87.9 mmol) prepared by conventional methods from (S)-(+)-2-methoxy-2-phenylacetic acid in CH2Cl2(250 mL) was added to the hot reaction mixture over 40 min. The resulting reaction mixture was boiled under reflux for further 1 h. The cooled reaction mixture was evaporated in vacuoand subjected to flash chromatography (silica gel, eluent: n-heptane/ethyl acetate/acetic acid = 55:45:1) to give (RS)-ethyl 2-[N-(2-methoxy-2-phenylacetamido)]-3-[3-hydroxy-5-(2-thienyl)isoxazol-4-yl]propionate (27.2 g; 81 %).
  • 30
  • [ 1030029-46-9 ]
  • [ 26164-26-1 ]
  • [ 1030029-49-2 ]
YieldReaction ConditionsOperation in experiment
98% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃;
  • 31
  • [ 1022985-32-5 ]
  • [ 26164-26-1 ]
  • [ 1022985-37-0 ]
YieldReaction ConditionsOperation in experiment
100% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3.5h;
100% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3.5h; Compound 2b (13.8 mg, 0.094 mmol) was dissolved in dichloromethane (1.0 mL). Then (s)-2-methoxy-2-phenylacetic acid (MPA) (17.1 mg, 0.10 mmol), EDCI.HCl (19.8 mg, 0.10 mmol) and a catalytic amount of DMAP were successively added. The mixture was stirred 3.5 h at room temperature. Then the mixture was concentrated and purified via column chromatography eluting with EtOAc/hexane to give the (S)-MPA ester in quantitative yield. 1H (CDCl3, 300 MHz) δ 7.45-7.31 (5H, m), 4.76 (1H, s), 4.33-4.19 (2H, m), 4.12, 4.01 (AB of ABX, JAB=11.3 Hz, JAX=4.5 Hz, JBX=6.6 Hz, 2H), 3.41 (3H, s), 2.01-1.78 (2H, m), 1.70-1.58 (1H, m), 1.30-1.19 (2H, m), 0.84 (3H, t, J=7.5 Hz).
  • 36
  • [ 26164-26-1 ]
  • [ 931-16-8 ]
  • [ 1093854-54-6 ]
  • [ 1093854-55-7 ]
YieldReaction ConditionsOperation in experiment
In methanol; at 65 - 70℃; Example 6 (Optical Resolution of Racemic Trans-2-Aminocyclohexanol with S-2-Methoxyphenylacetic Acid) To a 200 ml-volume four-neck flask equipped with a stirrer, a thermometer and a condenser were added 11.52 g (100 mmol) of racemic trans-2-aminocyclohexanol obtained in Reference Example 1, 16.62 g (25 mmol) of S-2-methoxyphenylacetic acid and 42.2 g of methanol, and heated to 70C. The mixture was aged at 65C for 1 hour and then cooled to 20 to 25C over 3 hours. After the mixture was stirred at the same temperature for 1 hour, the precipitated crystal was separated by filtration. The crystal was rinsed with 10.0 g of methanol and then dried to give 12.58 g of a salt. The content of trans-2-aminocyclohexanol in the salt was 40.9%. The resulting (1R,2R)-trans-2-aminocyclohexanol had an optical purity of 76.2% ee and a yield of 78.8%. To a 100 ml-volume four-neck flask equipped with a stirrer, a thermometer and a condenser were added 12.27 g (44 mmol) of the resulting crystal and 37.5 g of methanol, and heated to 70C. The mixture was aged at 65C for 1 hour and then cooled to 20 to 25C over 3 hours. After the mixture was stirred at the same temperature for 1 hour, the precipitated crystal was separated by filtration. The crystal was rinsed with 4.4 g of methanol and then dried to give 9.67 g of an S-2-methoxyphenylacetic acid salt of (1R,2R)-trans-2-aminocyclohexanol. The optical purity of the (1R,2R) isomer was at least 99% ee. 1H-NMR (400 MHz, D2O)delta: 7.22-7.29 (m, 5H), 4.48 (s, 1H), 3.32 (dt, 1H, J = 4.0 Hz, 10.2 Hz), 3.20 (s, 3H), 2.77 (dt, 1H, J = 4.4 Hz, 10.8 Hz), 1.86 (d, 2H, J = 12.0 Hz), 1.56 (d, 2H, J = 5.6 Hz), 1.06-1.25 (m, 4H). Specific rotation [alpha]D = 4.7 (c = 5, water, 25C). Melting point 189-191C (decomposition). The filtration mother liquor was concentrated, and the precipitated crystal was separated by filtration. The resulting crystal was repeatedly recrystallized to give an S-2-methoxyphenylacetic acid salt of (1S,2S)-trans-2-aminocyclohexanol with an optical purity of at least 99.5% ee. 1H-NMR (400 MHz, D2O)delta: 7.24-7.31 (m, 5H), 4.50 (s, 1H), 3.34 (dt, 1H, J = 4.0 Hz, 10.4 Hz), 3.22 (s, 3H), 2.79 (dt, 1H, J = 4.0 Hz, 11.0 Hz), 1.86 (d, 2H, J = 11.6 Hz), 1.58 (d, 2H, J = 6.4 Hz), 1.08-1.24 (m, 4H). Specific rotation [alpha]D = 8.3 (c = 5, water, 25C). Melting point 159-161C (decomposition).
  • 37
  • [ 1000698-88-3 ]
  • [ 88333-03-3 ]
  • [ 26164-26-1 ]
  • [ 2043-61-0 ]
  • C35H41F2N3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; at 20℃; To a mixture of (2-amino-4,5-difluoro-phenyl)-carbamic acid tert-butgamma ester (1.00 g, 4 mmol, 1.0 equiv) and (S)-alpha-methoxyphenylacetic acid (0.68 g, 1.0 equiv., [CAS RN 26164-26-1]) in methanol (25 mL) were added cyclohexanecarbaldehyde (0.459 g, 4 mmol, 1.0 equiv; [2043-61-0]) and benzyl isonitrile (0.48 g, l.Oequiv., 4 mmol, CAS RN 10340-91- 7). The mixture was stirred overnight at room temperature. A solution of 4 M HCl in dioxane (3 mL) was added, and the reaction mixture stirred at room temperature overnight. The mixture was partitioned between water (100ml) and ethyl acetate (100ml). The phases were separated and the aqueous phase extracted with ethyl acetate (2x50ml), the combined organic phases washed with brine, dried over sodium sulfate and evaporated under reduced pressure to afford the title compound as an orange gum (2.16g, quant., mixture of diastereomers) that was used without further purification. MS (ISP): 504.1 [M+H]+.
  • 38
  • [ 26164-26-1 ]
  • [ 163837-32-9 ]
  • [ 1246755-19-0 ]
YieldReaction ConditionsOperation in experiment
78% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;
  • 39
  • [ 26164-26-1 ]
  • [ 3728-20-9 ]
  • [ 1260612-39-2 ]
  • 40
  • 2C2HF3O2*C25H27N5O3 [ No CAS ]
  • [ 26164-26-1 ]
  • (2S,2'S)-N,N'-(1,3-oxazole-2,5-diyldi-4,1-phenylene)bis(1-((2S)-2-methoxy-2-phenylacetyl)-2-pyrrolidinecarboxamide) [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h; JG-19 HATU (48 mg, 0.128mmol)) was added in one portion to a stirred solution of JG-7b (30 mg, 0.058mmol), diisopropylethylamine (0.045 ml, 0.350 mmol) and (S)- (+)-methoxyphenyl acetic acid (21 mg, 0.128mmol) in anhydrous dimethylformamide (1.5mL) at room temperature. The mixture was stirred for 16h. Solvents were removed in vacuo and residue was purified by preparatory HPLC on Ci8- reverse phase to afford JG-19 as a yellow solid, 12.8 mg ( 30% yield). LRMS: Anal. Calc. for [M+H]+ C43H44N5O7: 742.8; found 742.5.
  • 41
  • [ 96-13-9 ]
  • [ 26164-26-1 ]
  • C12H14Br2O3 [ No CAS ]
  • C12H14Br2O3 [ No CAS ]
  • 42
  • [ 1345025-26-4 ]
  • [ 26164-26-1 ]
  • [ 1345025-31-1 ]
  • [ 1345025-28-6 ]
YieldReaction ConditionsOperation in experiment
1: 35% 2: 38% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; 4.5. Derivatization of (+/-)-7 with (S)-MPA To a solution of (+/-)-7 (1 g, 1.7 mmol) and (S)-methoxyphenyl acetic acid (0.40 g, 2.38 mmol) in dichloromethane (15 mL) were added 1,3-dicyclohexylcarbodiimide (0.49 g) and a catalytic amount of dimethylaminopyridine at room temperature. The resulting mixture was stirred for 1 h, then filtered and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography (5% ethanol in diethyl ether) to afford the less polar compound 8 (430 mg, 35%) and the more polar compound 9 (470 mg, 38%).
  • 43
  • [ 14235-81-5 ]
  • [ 26164-26-1 ]
  • [ 1360474-12-9 ]
YieldReaction ConditionsOperation in experiment
87% Stage #1: (S)-2-methoxy-2-phenylacetic acid With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; HATU In dichloromethane for 0.166667h; Stage #2: 4-Ethynylaniline In dichloromethane for 24h;
83% Stage #1: (S)-2-methoxy-2-phenylacetic acid With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; HATU In dichloromethane for 0.166667h; Stage #2: 4-Ethynylaniline In dichloromethane for 24h;
83% Stage #1: (S)-2-methoxy-2-phenylacetic acid With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 0.166667h; Stage #2: 4-Ethynylaniline In dichloromethane at 20℃; for 24h;
81% Stage #1: (S)-2-methoxy-2-phenylacetic acid With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane for 0.166667h; Stage #2: 4-Ethynylaniline In dichloromethane

  • 44
  • erythro-methyl 7,8-dihydroxytetradecanoate [ No CAS ]
  • [ 26164-26-1 ]
  • [ 1352404-14-8 ]
  • [ 1352404-40-0 ]
YieldReaction ConditionsOperation in experiment
1: 32% 2: 42% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; 4.5.6. (7R,8S)- and (7S,8R)-Methyl 7,8-bis((S)-2-methoxy-2-phenylacetoxy)tetradecanoates (7R,8S)-21 and (7S,8R)-21 To a solution of dihydroxyester mixture erythro-6 (45 mg, 0.16 mmol) in anhydrous CH2Cl2 (3 mL) under a N2 atmosphere was added DCC (135 mg, 0.65 mmol), DMAP (80 mg, 0.65 mmol) and (S)-methoxyphenylacetic acid (110 mg, 0.66 mmol) and the resulting solution was stirred at room temperature overnight. After filtration of the precipitate and removal of the CH2Cl2 in vacuo, the crude material (45:55 mixture of two diastereomers, >99% ee, 10% de) was subjected to preparative separation by enantioselective HPLC (Chiralpak AD-H column, 10% isopropanol in hexane, flow rate 10 mL min-1, UV detector 254 nm, retention times: (7R,8S)-21 22.8 min, (7S,8R)-21 28.6 min). Both diastereomers were obtained optically pure (>99% de and ee; 74% combined yield) and their absolute configurations were determined by NMR spectroscopy.Comment(7R,8S)-21: 30 mg, 53 μmol, 32%. Colourless oil. (c 0.34, CHCl3). 1H NMR (400 MHz, CDCl3) δ 0.51-0.73 (m, 2H), 0.79-0.96 (m, 2H), 0.89 (t, J = 6.8 Hz, 3H, H3-14), 1.02-1.34 (m, 12H), 1.43-1.54 (m, 2H), 2.08 (t, J = 7.6 Hz, 2H, H2-2), 3.42 (s, 3H), 3.43 (s, 3H), 3.68 (s, 3H), 4.46 (s, 1H), 4.75 (dt, J = 10.0, 3.5 Hz, 1H, H-7), 4.77 (s, 1H), 5.14 (dt, J = 8.6, 4.2 Hz, 1H, H-8), 7.25-7.33 (m, 5H), 7.36-7.41 (m, 3H), 7.46-7.49 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 14.0, 22.5, 24.0, 24.4, 25.3, 27.5, 28.3, 28.9, 30.2, 31.5, 33.7, 51.4 (RCO2CH3), 57.3, 57.5, 74.4, 74.7, 82.1, 82.5, 127.1 (2C), 127.3 (2C), 128.4 (2C), 128.5 (2C), 128.6, 128.7, 136.4, 136.5, 170.1, 170.3, 174.0 (C-1). 1H NMR (400 MHz, C6D6) δ 0.64-0.99 (m, 3H), 0.86 (t, J = 7.2 Hz, 3H, H3-14), 1.05-1.47 (m, 15H), 1.96 (t, J = 7.5 Hz, 2H, H2-2), 3.24 (s, 3H), 3.36 (s, 3H), 3.38 (s, 3H), 4.59 (s, 1H), 4.71 (s, 1H), 4.94 (dt, J = 10.3, 3.2 Hz, 1H, H-7), 5.39 (dt, J = 9.8, 3.5 Hz, 1H, H-8), 7.06-7.18 (m, 6H), 7.46 (br d, J = 8.0 Hz, 2H), 7.57 (br d, J = 8.0 Hz, 2H). HRMS ESI calcd for C33H46NaO8 ([M+Na]+): 593.3090. Observed: 593.3092.Comment(7S,8R)-21: 39 mg, 68 μmol, 42%. Colourless oil. (c 0.70, CHCl3). 1H NMR (400 MHz, CDCl3) δ 0.55-0.71 (m, 2H), 0.82 (t, J = 7.4 Hz, 3H, H3-14), 0.85-0.96 (m, 2H), 1.03-1.18 (m, 4H), 1.24-1.35 (m, 4H), 1.46-1.62 (m, 4H), 2.29 (t, J = 7.6 Hz, 2H, H2-2), 3.42 (s, 3H), 3.43 (s, 3H), 3.69 (s, 3H), 4.48 (s, 1H), 4.76 (dt, J = 9.4, 3.7 Hz, 1H, H-8), 4.78 (s, 1H), 5.13 (dt, J = 8.4, 4.0 Hz, 1H, H-7), 7.27-7.32 (m, 5H), 7.37-7.41 (m, 3H), 7.46-7.49 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 14.0 (C-14), 22.3, 24.3, 24.6, 25.0, 27.8, 28.5, 28.7, 30.0, 31.3, 33.8, 51.5 (RCO2CH3), 57.3, 57.5, 74.3, 74.8, 82.1, 82.5, 127.1 (2C), 127.3 (2C), 128.4 (2C), 128.5, 128.6 (2C), 128.7, 136.3, 136.4, 170.2, 170.3, 174.0 (C-1). 1H NMR (400 MHz, C6D6) δ 0.75-1.06 (m, 7H), 0.85 (t, J = 7.3 Hz, 3H, H3-14), 1.11-1.23 (m, 4H), 1.27-1.44 (m, 7H), 2.03 (t, J = 7.4 Hz, 2H, H2-2), 3.25 (s, 3H), 3.36 (s, 3H), 3.38 (s, 3H), 4.61 (s, 1H), 4.71 (s, 1H), 4.97 (dt, J = 10.3, 3.2 Hz, 1H, H-7), 5.35 (dt, J = 9.8, 3.5 Hz, 1H, H-8), 7.03-7.18 (m, 6H), 7.48 (br d, J = 8.0 Hz, 2H), 7.57 (br d, J = 8.0 Hz, 2H). HRMS ESI calcd for C33H46NaO8 ([M+Na]+): 593.3090. Observed: 593.3103.
  • 45
  • [ 1393082-57-9 ]
  • [ 26164-26-1 ]
  • [ 1393082-63-7 ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 20h; 4.13. Preparation of Mosher's esters of 9-(S)-11-(S) General procedure: A solution of (R)-α-methoxy-α-phenylacetic acid (MPA, 12.0 mg), 4-dimethylaminopyridine (DMAP, 10.0 mg), and N,N-dicyclohexylcarbodiimide (DCC, 10.0 mg) in CH2Cl2 (1.0 mL) was added to compound 9-(S) (5.0 mg) in CH2Cl2 (1.5 mL). The solution was stirred for 20 h at 25 °C, treated with EtOAc (30.0 mL) and filtered. The filtrate was concentrated and the residue purified by silica gel CC eluted with cyclohexane-EtOAc (95:5) to give 16-(S,R) (5.5 mg, 71%). Similarly, treatment of 9-(S) (5.0 mg) with (S)-MPA yielded 16-(S,S) (6.0 mg, 78%). Using the same method, esterification of 10-(S) and 11-(S) with (R)-MPA and (S)-MPA gave two pairs of Mosher's esters 17-(S,R)/17-(S,R) and 18-(S,R)/18-(S,S), respectively.
  • 46
  • [ 1393082-55-7 ]
  • [ 26164-26-1 ]
  • [ 1393082-59-1 ]
YieldReaction ConditionsOperation in experiment
78% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 20h; 4.13. Preparation of Mosher's esters of 9-(S)-11-(S) General procedure: A solution of (R)-α-methoxy-α-phenylacetic acid (MPA, 12.0 mg), 4-dimethylaminopyridine (DMAP, 10.0 mg), and N,N-dicyclohexylcarbodiimide (DCC, 10.0 mg) in CH2Cl2 (1.0 mL) was added to compound 9-(S) (5.0 mg) in CH2Cl2 (1.5 mL). The solution was stirred for 20 h at 25 °C, treated with EtOAc (30.0 mL) and filtered. The filtrate was concentrated and the residue purified by silica gel CC eluted with cyclohexane-EtOAc (95:5) to give 16-(S,R) (5.5 mg, 71%). Similarly, treatment of 9-(S) (5.0 mg) with (S)-MPA yielded 16-(S,S) (6.0 mg, 78%). Using the same method, esterification of 10-(S) and 11-(S) with (R)-MPA and (S)-MPA gave two pairs of Mosher's esters 17-(S,R)/17-(S,R) and 18-(S,R)/18-(S,S), respectively.
  • 47
  • [ 26164-26-1 ]
  • (S)-12-hydroxyhexadecanoic acid methyl ester [ No CAS ]
  • [ 1393082-61-5 ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 20h; 4.13. Preparation of Mosher's esters of 9-(S)-11-(S) General procedure: A solution of (R)-α-methoxy-α-phenylacetic acid (MPA, 12.0 mg), 4-dimethylaminopyridine (DMAP, 10.0 mg), and N,N-dicyclohexylcarbodiimide (DCC, 10.0 mg) in CH2Cl2 (1.0 mL) was added to compound 9-(S) (5.0 mg) in CH2Cl2 (1.5 mL). The solution was stirred for 20 h at 25 °C, treated with EtOAc (30.0 mL) and filtered. The filtrate was concentrated and the residue purified by silica gel CC eluted with cyclohexane-EtOAc (95:5) to give 16-(S,R) (5.5 mg, 71%). Similarly, treatment of 9-(S) (5.0 mg) with (S)-MPA yielded 16-(S,S) (6.0 mg, 78%). Using the same method, esterification of 10-(S) and 11-(S) with (R)-MPA and (S)-MPA gave two pairs of Mosher's esters 17-(S,R)/17-(S,R) and 18-(S,R)/18-(S,S), respectively.
  • 48
  • [ 1384933-63-4 ]
  • [ 26164-26-1 ]
  • [ 1384933-65-6 ]
  • [ 1384933-64-5 ]
YieldReaction ConditionsOperation in experiment
1: 36% 2: 35% With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 24h; Inert atmosphere; 4 4.4 (+)- and (-)-2-(4-Fluorophenyl)-3-nitro-8-[(S)-α-methoxyphenylacetoxy]-2H-chromene (+)-4a and (-)-4b To a stirred solution of 3 (2.87 g, 10 mmol) in CHCl3 (80 mL) were added (S)-(+)-α-methoxyphenylacetic acid (2.5 g, 15 mmol), DMAP (0.5 g, 4 mmol), and DCC (3.1 g, 15 mmol). The mixture was stirred at room temperature for 24 h. After filtration, the filtrate was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography (CH2Cl2/Et2O, 10:1) to give (+)-4a (1.6 g, 36%) and (-)-4b (1.52 g, 35%), respectively. (+)-4a: Pale yellow solid, mp 103-105 °C (10% AcOEt in hexane); [α]20D=+282[α]D20=+282 (c 0.11, CHCl3); 1H NMR (600 MHz, CDCl3): δ 8.03 (s, 1H), 7.50-7.51 (m, 2H), 7.43-7.44 (m, 3H), 7.24 (d, J = 7.8 Hz, 1H), 7.07-7.11 (m, 3H), 7.01 (d, J = 7.8 Hz, 1H), 6.96-6.99 (m, 2H), 6.34 (s, 1H), 5.02 (s, 1H), 3.50 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 168.1, 163.3 (J = 247.8 Hz), 144.9, 141.5, 138.8, 135.5, 132.0 (J = 2.9 Hz), 129.1, 128.9 (J = 8.3 Hz), 128.7 (2C), 128.5, 128.0, 127.6, 127.3 (2C), 122.5, 119.3, 115.8 (J = 21.8 Hz), 82.2, 73.8, 57.5; ESI-MS (m/z): 436.5 [M+H]+, 453.5 [M+NH4]+, 458.5 [M+Na]+. (-)-4b: Pale yellow solid, mp 135-137 °C (10% AcOEt in hexane); [α]20D=-112.5[α]D20=-112.5 (c 0.16, CHCl3); 1H NMR (600 MHz, CDCl3): δ 8.05 (s, 1H), 7.56-7.57 (m, 2H), 7.45-7.47 (m, 3H), 7.23-7.24 (d, J = 7.8 Hz, 1H), 7.07 (d, J = 7.8 Hz, 1H), 7.00 (t, J = 7.8 Hz, 1H), 6.88-6.93 (m, 4H), 6.34 (s, 1H), 4.99 (s, 1H), 3.46 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 168.0, 163.2 (J = 247.5 Hz), 144.8, 141.5, 138.9, 135.7, 131.7 (J = 3.3 Hz), 129.2, 128.8 (J = 8.3 Hz), 128.74 (2C), 128.72, 128.0, 127.8 (2C), 127.5, 122.6, 119.5, 115.6 (J = 21.6 Hz), 82.3, 73.4, 57.5; ESI-MS (m/z): 436.5 [M+H]+, 453.5 [M+NH4]+, 458.5 [M+Na]+.
  • 49
  • [ 1428654-14-1 ]
  • [ 26164-26-1 ]
  • [ 1428377-58-5 ]
YieldReaction ConditionsOperation in experiment
88% With dmap; 2-methyl-6-nitrobenzoic anhydride; triethylamine In dichloromethane at 20℃; for 6h; 6 3.7 Conversion of 1 into di-(S)-α-methoxyphenylacetate 4b General procedure: To a solution of 1 (1.1 mg, 1.9 μmol) in dichloromethane (0.5 mL) were added triethylamine (20 μL), DMAP (2.9 mg), 2-methyl-6-nitrobenzoic anhydride (8.2 mg), and (R)-α-methoxyphenylacetic acid (7.1 mg) at room temperature. After being stirred for 6 h, the mixture was poured into saturated ammonium chloride solution, and extracted with ethyl acetate three times. The combined organic layer was washed with water and brine, dried over sodium sulfate, and evaporated. The residue was chromatographed over silica gel eluted by hexane/ethyl acetate (1:1) to give 4a (1.2 mg, 1.4 μmol, 72%). In the same manner as the synthesis of 4a, compound 4b (1.2 mg, 1.4 μmol, 88%) was synthesized from 1. Data for 4b: colorless oil; 1H NMR (600 MHz, CDCl3) δ 7.43-7.45 (4H, m), 7.29-7.38 (6H, m), 4.89-4.91 (1H, m), 4.72 (1H, s), 4.69 (1H, s), 4.49 (1H, dd, J=11.6, 4.3 Hz), 4.11 (1H, dd, J=12.1, 2.3 Hz), 4.02-4.07 (2H, m), 3.40 (3H, s), 3.38 (3H, s), 2.03 (3H, s), 2.02 (3H, s), 1.94-1.99 (2H, m), 1.14-1.81 (18H, m), 1.03 (1H, dd, J=12.7, 2.0 Hz), 0.94 (3H, s), 0.92 (3H, s), 0.91 (3H, s), 0.84 (3H, s), 0.68 (3H, s), 0.65 (3H, s), 0.42 (3H, s); HRFABMS: m/z 872.5032 [M]+ (872.5071 calcd for C52H72O11).
  • 50
  • [ 1361550-98-2 ]
  • [ 26164-26-1 ]
  • [ 1361551-18-9 ]
YieldReaction ConditionsOperation in experiment
73% With dmap; dicyclohexyl-carbodiimide at 20℃; for 15h; Inert atmosphere; (2S,2'S')-((2S,3S,4E,6E)-8-Ethoxy-7-methyl-8-oxoocta-4,6-diene-2,3-diyl) bis(2-methoxy-2-phenylacetate) (SI18) To a solution of 13 (18 mg, 0.084 mmol) were added (S)-2-methoxy-2-phenylacetic acid (54 mg, 0.32 mmol, 3.9 eq.), DMAP (10 mg, 0,084 mmol, 1 eq.), CSA (15 mg, 0.065 mmol, 0.8 eq.) and DCC (69 mg, 0.33 mmol, 3.9 eq.). The reaction mixture was stirred at room temperature for 15 h, before being filtered, concentrated under reduced pressure and purified by preparative TLC (heptane/ethyl acetate 70:30). SI18 (31 mg, 0.061 mmol, 73 %, d.e: 93:7) was obtained as colorless oil.; 1H NMR (CDCl3, 300 MHz) δ 7.45-7.31 (10H), 7.29 (d, J = 13.8 Hz, 1H), 6.78 (dd, J = 1.2, 11.7 Hz, 1H), 6.28 (dd, J = 11.7, 13.8 Hz, 1H), 5.35(m,1H), 5.01 (dd, J = 3.7, 6.5 Hz, 1H), 4.72 (s, 1H), 4.67 (s, 1H), 4.22 (q,J = 7 Hz, 2H), 3.36 (s, 3H), 3.33 (s, 3H), 1.81 (dd, J = 1.2 Hz, 3H), 1.33 (t, J = 7.2 Hz, 3H), 0.94 (d, J = 6.5 Hz, 3H).; 13C NMR (CDCl3. 75 MHz) δ 169.7, 169.6, 167.9, 136.2, 136.1, 136.0, 132.5, 129.2, 129.1, 128.9, 128.8, 128.6 (4xC), 127.2 (2xC), 127.1 (2xC), 82.4, 82.2, 75.1, 71.1, 60.7, 57.3, 57.2, 15.6, 14.3, 12.7.
  • 51
  • [ 26164-26-1 ]
  • C11H18O4 [ No CAS ]
  • [ 1361551-18-9 ]
YieldReaction ConditionsOperation in experiment
73% With dmap; (1S)-10-camphorsulfonic acid; dicyclohexyl-carbodiimide at 20℃; for 15h; SI18 (2S,2'S)-((2S,3S,4E,6E)-8-Ethoxy-7-methyl-8-oxoocta-4,6-diene-23- diyl) bis(2-methoxy-2-phenylacetate) (SI18) (2S,2rS)-((2S,JS,^E,6E)-8-Ethoxy-7-methyl-8-oxoocta-4,6-diene-23- diyl) bis(2-methoxy-2-phenylacetate) (SI18)To a solution of 13 (18 mg, 0.084 mmol) were added (S)-2-methoxy-2- phenylacetic acid (54 mg, 0.32 mmol, 3.9 eq.), DMAP (10 mg, 0,084 mmol, 1 eq.), CSA (15 mg, 0.065 mmol, 0.8 eq.) and DCC (69 mg, 0.33 mmol, 3.9 eq.). The reaction mixture was stirred at room temperature for 15 h, before being filtered, concentrated under reduced pressure and purified by preparative TLC (heptane/ethyl acetate 70:30). SI18 (31 mg, 0.061 mmol, 73 %, d.e: 93:7) was obtained as colorless oil.1H NMR (CDCI3, 300 MHz) ? 7.45-7.31 (10H),7.29 (d, J = 13.8 Hz, 1H), 6.78 (dd, J - 1.2, 1 1.7 Hz, 1H), 6.28 (dd, J = 11.7, 13.8 Hz, 1H), 5.35(m,lH), 5.01 (dd, J = 3.7, 6.5 Hz, 1H), 4.72 (s, 1H), 4.67 (s, 1H), 4.22 (q,J = 7 Hz, 2H), 3.36 (s, 3H), 3.33 (s, 3H), 1.81 (dd, J= 1.2 Hz, 3H), 1.33 (t, J = 7.2 Hz, 3H), 0.94 (d, J= 6.5 Hz, 3H).13C NMR {CDClj. 75 MHz) ? 169.7, 169.6, 167.9, 136.2, 136.1, 136.0, 132.5, 129.2, 129.1, 128.9, 128.8, 128.6 (4xQ, 127.2 (2xC), 127.1 (2xC), 82.4, 82.2, 75.1, 71.1, 60.7, 57.3, 57.2, 15.6, 14.3, 12.7.
  • 52
  • [ 26164-26-1 ]
  • [ 1449375-07-8 ]
  • [ 1449375-12-5 ]
YieldReaction ConditionsOperation in experiment
90% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; 3.3.2. General procedure for the esterification. General procedure: To a solution of analcohol (1.0 equiv) in CH2Cl2 (30 mL/mmol) were added DCC (1.2 equiv), DMAP (0.2 equiv), and (R)- or (S)-methoxyphenylacetic acid (1.5 equiv). The mixture was stirred overnight at room temperature and the cloudy solution was filtered on cotton. The solution was then washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (PE/Et2O: 100:0e7:3) to afford the corresponding ester.
  • 53
  • [ 26164-26-1 ]
  • [ 225114-87-4 ]
  • [ 1477482-31-7 ]
YieldReaction ConditionsOperation in experiment
95% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.5h;
80% With dmap; dicyclohexyl-carbodiimide In dichloromethane for 0.75h; Mandelate ester of racemic alcohol-17 To a solution of the racemic alcohol 17 (30 mg, 0.07 mmol, 1 eq) in anhydrous CH2Cl2(1.5 mL) (S)-O-methyl mandelic acid (43.2 mg, 0.07 mmol, 1 eq), DCC (64.4 mg, 0.09mmol, 1.2 eq), and a few crystals of DMAP were added and the mixture was stirred for45 min. The solvent was removed under reduced pressure and the residue was purifiedby flash column chromatography on silica gel using petroleum ether as the eluent toafford a diastereomeric mixture of esters (37.4 mg, 0.06 mmol) in 92% yield
  • 54
  • [ 26164-26-1 ]
  • [ 225114-80-7 ]
  • C33H42O4Si2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With dmap; dicyclohexyl-carbodiimide In dichloromethane for 0.75h; Mandelate ester of racemic alcohol-17 To a solution of the racemic alcohol 17 (30 mg, 0.07 mmol, 1 eq) in anhydrous CH2Cl2(1.5 mL) (S)-O-methyl mandelic acid (43.2 mg, 0.07 mmol, 1 eq), DCC (64.4 mg, 0.09mmol, 1.2 eq), and a few crystals of DMAP were added and the mixture was stirred for45 min. The solvent was removed under reduced pressure and the residue was purifiedby flash column chromatography on silica gel using petroleum ether as the eluent toafford a diastereomeric mixture of esters (37.4 mg, 0.06 mmol) in 92% yield
  • 55
  • [ 26164-26-1 ]
  • [ 1637662-96-4 ]
  • [ 1607814-47-0 ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Synthesis of the MPA esters 1r, 1s, 15r, 15s The acid (1 or 15) was dissolved in MeOH (1 mL) and treatedwith a solution of TMSCH2N2 2.0 M in Et2O (100 lL). After stirringthe mixture at room temp. for 30 min, the solvent was evaporated.Treatment of 1 (2.8 mg, 0.011 mmol) and 15 (7.1 mg, 0.022 mmol)as described above yielded the methyl esters 1a and 15a, respectively,with quantitative yield in both cases. Each methyl esterwas dissolved in CH2Cl2 (0.5 mL) and treated with CH2Cl2 solutions(0.5 mL each) of N,N0-dicyclohexylcarbodiimide (tenfold excessover the starting compound), N,N-dimethylaminopyridine (fivefoldexcess) and the MPA acid (fivefold excess). The mixture was stirredovernight at room temp. and then purified by preparative TLC(hexanes-EtOAc 85:15, v/v) to obtain the MPA ester. Treatmentof 1a (1.6 mg, 5.8 103 mmol) and 15a (5.4 mg, 1.6 102mmol) with (R)-MPA as described above yielded compounds 1rand 15r, respectively. Treatment of 1a (1.2 mg, 4.3 103 mmol)and 15a (1.7 mg, 5.1 103 mmol) with (S)-MPA as describedabove yielded compounds 1s and 15s, respectively.
  • 56
  • [ 26164-26-1 ]
  • [ 151675-39-7 ]
  • [ 1607814-49-2 ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Synthesis of the MPA esters 1r, 1s, 15r, 15s The acid (1 or 15) was dissolved in MeOH (1 mL) and treatedwith a solution of TMSCH2N2 2.0 M in Et2O (100 lL). After stirringthe mixture at room temp. for 30 min, the solvent was evaporated.Treatment of 1 (2.8 mg, 0.011 mmol) and 15 (7.1 mg, 0.022 mmol)as described above yielded the methyl esters 1a and 15a, respectively,with quantitative yield in both cases. Each methyl esterwas dissolved in CH2Cl2 (0.5 mL) and treated with CH2Cl2 solutions(0.5 mL each) of N,N0-dicyclohexylcarbodiimide (tenfold excessover the starting compound), N,N-dimethylaminopyridine (fivefoldexcess) and the MPA acid (fivefold excess). The mixture was stirredovernight at room temp. and then purified by preparative TLC(hexanes-EtOAc 85:15, v/v) to obtain the MPA ester. Treatmentof 1a (1.6 mg, 5.8 103 mmol) and 15a (5.4 mg, 1.6 102mmol) with (R)-MPA as described above yielded compounds 1rand 15r, respectively. Treatment of 1a (1.2 mg, 4.3 103 mmol)and 15a (1.7 mg, 5.1 103 mmol) with (S)-MPA as describedabove yielded compounds 1s and 15s, respectively.
  • 57
  • [ 26164-26-1 ]
  • [ 90673-37-3 ]
  • 1-((2S)-2-methoxy-2-phenylacetyl)-7-methyl-1,4-diazepan-5-one [ No CAS ]
  • 58
  • [ 26164-26-1 ]
  • 3-(5-amino-1H-indazol-3-yl)benzenesulfonamide 2,2,2-trifluoroacetate [ No CAS ]
  • [ 1338818-06-6 ]
YieldReaction ConditionsOperation in experiment
59% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; 4.2.1.1 Method A (amide coupling) General procedure: A DMF solution of 3-(5-amino-1H-indazol-3-yl)benzenesulfonamide 2,2,2-trifluoroacetate (1.0equiv), DIPEA (N,N-diisopropylethylamine, 3equiv) and RCO2H (1.05equiv) at 0°C was treated with TBTU (O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate) (1.05equiv) added in one portion. The reaction was stirred allowing slowly to warm to rt. After several hours or overnight stirring the crude reaction was purified directly by preparative HPLC. Alternatively, a DMF solution of 3-(3-sulfamoylphenyl)-1H-indazole-5-carboxylic acid (1.0equiv), DIPEA (3equiv) and RR′NH (1.05equiv) at 0°C or rt was treated with TBTU (1.05equiv) added in one portion. The reaction was stirred allowing slowly to warm to rt. After several hours or overnight stirring the crude reaction was purified directly by prepHPLC.
  • 59
  • [ 26164-26-1 ]
  • (S)-(+)-1-(10H-phenothiazin-10-yl)propan-2-ol [ No CAS ]
  • C24H23NO3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h; General procedure for the determination of the absolute configuration of (S)-(+)-5Esterification of (S)-(+)-1-(10H-phenothiazin-10-yl)propan-2-ol (S)-(+)-5 with (R)- or (S)-α-methoxy-α-phenylacetic acid General procedure: A catalytic amount of DMAP (5 mg) was added to a solution of enantiopure (S)-(+)-1-(10H-phenothiazin-10-yl)propan-2-ol (S)-(+)-5 (100 mg, 0.39 mmol, >99% ee), (R)- or (S)-α-methoxy-α-phenylacetic acid (65 mg, 0.39 mmol) as appropriate, and DCC (96 mg, 0.47 mmol) in anhydrous CH2Cl2 (3 mL). After 24 h of stirring at room temperature, precipitated dicyclohexylurea was removed by filtration and then the urea cake was rinsed with CH2Cl2 (10 mL). The combined CH2Cl2 solutions were evaporated to dryness, and the crude product was purified by preparative layer chromatography using a mixture of hexane/AcOEt (50:10, v/v) as an eluent. Appropriately, the separated fraction was removed from the plate together with SiO2 gel, placed in a round-bottomed flask, and stirred along with mixture of hexane/AcOEt (100 mL; 1:1, v/v) for over 1 h. Finally, silica gel was filtered off, the fraction was rinsed with AcOEt (50 mL), and the resulting filtrate was evaporated to dryness to afford the corresponding pure product 11 or 12.
  • 60
  • [ 50541-93-0 ]
  • [ 26164-26-1 ]
  • C21H26N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; 6.1 Step 1 Step 1: To a stirred solution of [19] (0.80g, 4.81mmol) in DMF (5.0ml) was added EDC (1.40g, 7.2 mmol), HOBT (0.97g, 7.2mmol) at room temperature. After an additional stirring for 5 minutes at same temperature, [20](l . l lml, 5.30mmol) and NMM (1.6ml, 14.43mmol) was added. The reaction temperature was allowed to stirred at room temperature for overnight. TLC showed complete consumption of starting material. Water (100 ml) was added and organic layer was extracted with ethyl acetate (2 x 100 ml). The combined organic layers were washed with water, brine and dried over sodium sulphate. The organic layer was concentrated to afford light yellow powder which was triturated with pentane to afford off white solid material [21] (1.20g, 75%).Analytical Data: [21] ESIMS: 339 [M++l].
  • 61
  • [ 41598-71-4 ]
  • [ 26164-26-1 ]
  • (S)-(S)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl-2-phenylpropanoate [ No CAS ]
  • (S)-(R)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl-2-phenylpropanoate [ No CAS ]
  • 62
  • [ 26164-26-1 ]
  • (R)-N2-(1-(pyridazin-3-yl)pyrrolidin-3-yl)-1,3,4-thiadiazole-2,5-diamine [ No CAS ]
  • (2S)-2-methoxy-2-phenyl-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With 2,4,6-trimethyl-pyridine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at 0 - 20℃; for 19h; Inert atmosphere;
18% With O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 17 - 30℃; for 16h; 2(a) Example 2(a)
(2S)-2-Methoxy-2-phenyl-N-[5- [[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino] -1,3,4-thiadiazol-2-yl]acetamide Example 2(a)(2S)-2-Methoxy-2-phenyl-N-[5- [[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino] -1,3,4-thiadiazol-2-yl]acetamideA mixture of ^-[(S^-l-pyridazin-S-ylpyrrolidin-S-ylJ-l^^-thiadiazole^^-diamine (Intermediate 5, 150 mg, 0.57 mmol), (2S)-2-methoxy-2-phenylacetic acid (174.4 mg, 0.57 mmol), HATU (325 mg, 0.86 mmol) and DIPEA (147 mg, 1.14 mmol) in DMF (3 mL) were stirred for 16 h at r.t. The crude reaction mixture was then purified by Prep- HPLC (column: SunFire Prep C18 OBD Column, 5μπι, 19mm xl 50mm; mobile phase: MeOH and water with 0.1% TFA, eluting with 25.0% water with 0.1% TFA up to 50.0% water with 0.1% TFA over an 8 minute period; detector, UV 220, 254nm). This delivered product (43 mg, 18%) as a white solid. 1H NMR (300 MHz, DMSO-d6, 26°C) δ 2.00-2.10 (1H, m), 2.23-2.49 (1H, m), 3.30 (3H, s), 3.45-3.57 (3H, m), 3.71-3.76 (1H, m), 4.33-4.38 (1H, m), 4.97 (1H, s), 6.87 (1H, d), 7.30-7.47 (6H, m), 7.69 (1H, d), 8.46 (1H, d), 12.22 (1H, br); m/z: ES+ [M+H]+ 412. Material prepared using the above method was analysed by XRPD and found to be amorphous, with a melting point of 82.1°C (onset). Slurrying experiments were carried out on the amorphous material by placing 20 mg in a vial with a magnetic stirrer bar, and then adding approximately 2 mL of a given solvent. The vial was then sealed tightly with a cap and the mixture left to stir on a magnetic stirrer plate. After approximately 3 days, the sample was removed from the plate, the cap taken off and the solvent left to evaporate under ambient conditions before analysis of the resultant solid by XRPD. Three forms (Types A, B and C) were distinguished and determined to be partially crystalline. Form A material was produced by slurrying in isopropyl alcohol as solvent at 25°C. Form B material was produced by slurrying in EtOAc as solvent at 25°C. Form C material was produced by slurrying in MeCN as solvent at 25°C. Form D material was produced by heating Form B or Form C material to 200°C before cooling to r.t. This form was determined to be crystalline by XRPD, with the following characteristic diffraction peaks. Single crystal X-Ray analysis was performed on the Form D material, confirming the compound to be a single diastereomer of the stereochemistry shown above.
  • 63
  • [ 26164-26-1 ]
  • N'-[(3R)-1-(1,2,4-triazin-6-yl)pyrrolidin-3-yl]-1,3,4-thiadiazole-2,5-diamine [ No CAS ]
  • (2S)-2-methoxy-2-phenyl-N-[5-[[(3R)-1-(1,2,4-triazin-6-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 1h; 3 Example 3
(2S)-2-methoxy-2-phenyl-N-[5-[[(3R)-1-(1,2,4-triazin-6-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Example 3(2S)-2-methoxy-2-phenyl-N-[5-[[(3R)-1-(1,2,4-triazin-6-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamideHATU (319 mg, 0.84 mmol) was added to iV-[(3R)-l-(l,2,4-triazin-6-yl)pyiTolidin-3-yl]- l,3,4-thiadiazole-2,5-diamine (Intermediate 9, 185 mg, 0.70 mmol), (2S)-2-methoxy-2- phenylacetic acid (1 16 mg, 0.70 mmol) and DIPEA (0.122 mL, 0.70 mmol) in DMF (5 mL) at 0°C. The resulting solution was stirred at 0°C for 1 h. The reaction mixture was diluted with MeOH (5 mL) and purified by ion exchange chromatography, using a 20g SCX column. The desired product was eluted from the column using 3M ammonia in MeOH, and pure fractions were evaporated to dryness to afford crude product. The crude product was purified by FCC, elution gradient 0 to 8% MeOH in DCM. Pure fractions were evaporated to dryness to afford (2S)-2-methoxy-2-phenyl-N-[5-[[(3 ?)-l-(l,2,4- triazin-6-yl)pyrrolidin-3-yl]amino]-l,3,4-thiadiazol-2-yl]acetamide (200 mg, 69%) as a white solid. 1H MR (400 MHz, DMSO-d6, 27°C) δ 2.02-2.13 (1H, m), 2.21-2.34 (1H, m), 3.30 (3H, s), 3.54 (1H, dd), 3.61 (2H, dd), 3.78 (1H, dd), 4.34-4.44 (1H, m), 4.97 (1H, s), 7.30-7.40 (3H, m), 7.45 (2H, dd), 7.68 (1H, d), 8.26 (1H, s), 8.94 (1H, s), 12.21 (1H, s); m/z: ES+ [M+H]+ 413.
  • 64
  • [ 26164-26-1 ]
  • (R)-2-(benzofuran-3-yl)-1-((3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)ethan-1-amine hydrochloride [ No CAS ]
  • (S)-N-((R)-(benzofuran-3-yl)-1-((1S,2S,6R,8S)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)ethyl)-2-methoxy-2-phenylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at -10℃; for 3h; Inert atmosphere; 33 (S^ -iiR^-ibenzofuran-S-y -l-iiSaS^S^SJaRJ-Sa.S.S-trimethylhexahyclro^.e- methanobenzo[d][1 ,3,2]dioxaborol-2-yl)ethyl)-2-methoxy-2-phenylacetamide: (S^ -iiR^-ibenzofuran-S-y -l-iiSaS^S^SJaRJ-Sa.S.S-trimethylhexahyclro^.e- methanobenzo[d][1 ,3,2]dioxaborol-2-yl)ethyl)-2-methoxy-2-phenylacetamide: To a solution of (Ri^-Benzofuran-S-yl-l-iilS^S.eR.eSJ^.Q.Q-trimethyl-S^-dioxa^- bora-tricyclo[6.1.1.02,6]dec-4-yl)-ethyl-aminehydrochloride (0.85mmol; 0.35g) in 15mL DMF was added (S)-Methoxy-phenyl-acetic acid (0.85 mmol; 0.14 g) at -10°C under nitrogen atmosphere. Then N-Ethyl-diisopropyl-amine (2.56 mmol; 0.45 ml) and [(Benzotriazol-1-yloxy)-dimethylamino-methylene]-dimethyl-ammonium tetrafluoroborate (TBTU) (1.02mmol; 0.33 g) were added. The solution was stirred for 3h at -10°C. The reaction mixture was diluted with ethyl acetate and brine. The organic phase was washed with brine (5x20 mL). The organic layer was dried over sodium sulfate, filtered, concentrated in vacuo (bath temperature 30°C) and purified by flash chromatography (silica gel, petroleum ether/ethyl acetate; gradient 0-50% ethyl acetate) to yield 0.3 g (53%) of the title compound as a pale green solid. HPLC MS (Agilent - Waters Xbridge C8 (50x4.6 mm, 3.5 pm); 254nm; buffer A: 0.1% TFA/H20, buffer B: 0.1% TFA/ACN; (0.0-8.0min 5%-100% buffer B; 8.0-8.1 min 100% buffer B; 8.1-8.5min 100%-5% buffer B; 8.5-10.Omin 5%-5% buffer B): (M+H) 488.0; Rt 6.24 min.
  • 65
  • [ 26164-26-1 ]
  • (2SR,3SR)-3-hydroxy-2-methyl-2-(4-methylpent-3-en-1-yl)chroman-6-carboxamide [ No CAS ]
  • (S)-(2S,3S)-6-carbamoyl-2-methyl-2-(4-methylpent-3-en-1-yl)chroman-3-yl 2-methoxy-2-phenylacetate [ No CAS ]
  • (S)-(2R,3R)-6-carbamoyl-2-methyl-2-(4-methylpent-3-en-1-yl)chroman-3-yl 2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 38% 2: 41% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; To a solution of 8 (76 mg, 0.26 mmol) in dry dichloromethane (8 ml), (S)-methoxyphenylaceticacid (48 mg, 0.29 mmol), dicyclohexylcarbodiimide (70 mg, 0.34 mmol) and 4-(dimethylamino)pyridine (4 mg, 0.0057 mmol) were added, and the mixture was stirred at roomtemperature for 1 h. Then, the reaction mixture was filtered, and the filtrate was concentratedunder reduced pressure. The residue was purified by column chromatography using DCM/AcOEt (20/1) as eluent affording 16 (44 mg, 38%) and 17 (47 mg, 41%) as colorless oils.
  • 66
  • [ 26164-26-1 ]
  • (2RS,3SR)-3-hydroxy-2-methyl-2-(4-methylpent-3-en-1-yl)chroman-6-carboxamide [ No CAS ]
  • (S)-(2S,3R)-6-carbamoyl-2-methyl-2-(4-methylpent-3-en-1-yl)chroman-3-yl 2-methoxy-2-phenylacetate [ No CAS ]
  • (S)-(2R,3S)-6-carbamoyl-2-methyl-2-(4-methylpent-3-en-1-yl)chroman-3-yl 2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 44% 2: 37% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; General procedure: To a solution of 8 (76 mg, 0.26 mmol) in dry dichloromethane (8 ml), (S)-methoxyphenylaceticacid (48 mg, 0.29 mmol), dicyclohexylcarbodiimide (70 mg, 0.34 mmol) and 4-(dimethylamino)pyridine (4 mg, 0.0057 mmol) were added, and the mixture was stirred at roomtemperature for 1 h. Then, the reaction mixture was filtered, and the filtrate was concentratedunder reduced pressure. The residue was purified by column chromatography using DCM/AcOEt (20/1) as eluent affording 16 (44 mg, 38%) and 17 (47 mg, 41%) as colorless oils.
  • 67
  • [ 26164-26-1 ]
  • (S)-1-aminoheptadeca-16-en-10,12-diyn-2-ol [ No CAS ]
  • C35H43NO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Inert atmosphere;
3.6 mg Stage #1: (S)-2-methoxy-2-phenylacetic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.333333h; Inert atmosphere; Stage #2: (S)-1-aminoheptadeca-16-en-10,12-diyn-2-ol In dichloromethane at 20℃; for 24h; Inert atmosphere; Acylation, Method B: General procedure: A solution of benzoic or 2-naphthoic acid (~1 mmol, 5 equiv), EDCHCl(5.5 equiv) and DMAP in CH2Cl2 was stirred at 0 C for 20 min under N2. A solution of 1-AA inCH2Cl2 was (final concentration of 1-AA ~0.01 M) and the mixture warmed to rt over 24 h. AdditionalCH2Cl2 (20 mL) was added and the mixture washed successively with equal volumes of 10% HCl,water, NaHCO3 (satd.) and H2O. After drying (Na2SO4), the volatiles were removed and the residuepurified by flash chromatography (silica), followed by HPLC (silica or RP C18) if required
  • 68
  • [ 26164-26-1 ]
  • 6-(1-methyl-1H-pyrazol-4-yl)-4-(6-(piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile dihydrochloride [ No CAS ]
  • C30H28N8O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
19.2% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; 84 (S)-4-(6-(4-(2-hydroxy-2-phenyl acetyl)piperazin- 1 -yl)pyridin-3 -yl)-6-(i -methyl-i Hpyrazol-4-yl)pyrazolo[1,5 -a]pyridine-3 -carbonitrile To a solution of 6-(i-methyl-1H-pyrazol-4-yl)-4-(6-(piperazin-i-yl)pyridin-3-yl)pyrazolo[i,5-a]pyridine-3-carbonitrile (15 mg, 0.0390 mmol) in DMF (390 tL) was added (S)2-methoxy-2-phenylacetic acid (9.73 mg, 0.0585 mmol), DMAP (14.3 mg, 0.117 mmol), and EDC-HC1 (11.6 mg, 0.0605 mmol). After stirring overnight at ambient temperature, the reaction mixture was diluted with MeOH and then purified directly using reverse phase chromatography (0-70% ACN/water) to provide the title compound (4.0 mg, i9.2% yield). MS (apci) m/z = 533.0 (M+H).
  • 69
  • [ 5405-41-4 ]
  • [ 26164-26-1 ]
  • C15H20O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; 1.27 4.1.27 (S)-Mandelate ester of rac 25 To a solution of racemic alcohol (33 mg, 0.25 mmol), obtained by treatment of ethyl acetoacetate with NaBH4, in DCM (1.0 mL) was added (S)-(-)-α-methoxy phenylacetic acid (45.5 mg, 0.275 mmol), DMAP (5 mg, 15 mol%) and DCC (62.3 mg, 0.275 mmol) at 0 °C. The reaction mixture was stirred for 2 h at rt and the solvent was evaporated in vacuo. The crude product was triturated with cold ether (2 mL) to afford the mandelate ester of the alcohol in 90% yield as mixture of diastereomer. TLC: Rf 0.3 (9:1 hexanes:ethyl acetate). 1H NMR (300 MHz, CDCl3): δ 7.45-7.40 (m, 4H), 7.39-7.30 (m, 6H), 5.40-5.26 (m, 2H), 4.74-4.71 (2s, 2H), 4.13-4.04 (m, 2H), 3.96-3.77 (m, 2H), 3.42-3.39 (2s, 6H), 2.69-2.36 (m, 4H), 1.32-1.16 (m, 9H), 1.09 (t, J = 6.8 Hz, 3H).
  • 70
  • [ 26164-26-1 ]
  • N2-[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]-1,3,4-thiadiazole-2,5-diamine [ No CAS ]
  • (2S)-N-[5-[[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-methoxy-2-phenylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
27.8% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 3h; Inert atmosphere; 2 Example 2 HOBT (120 mg, 0.78 mmol) was added to N2-[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]-1,3,4-thiadiazole-2,5-diamine (Intermediate 4, 220 mg, 0.78 mmol), (2S)-2-methoxy-2-phenyl-acetic acid (130 mg, 0.78 mmol) and EDC (300 mg, 1.56 mmol) in DMF (3 mL) at 25° C. The resulting mixture was stirred at 25° C. for 3 hours. The crude product was purified by preparative HPLC (XBridge C18 OBD column, 5 μm, 50 mm×150 mm). Decreasingly polar mixtures of water (containing 0.05% formic acid) and MeCN were used as a mobile phase. Fractions containing the desired compound were evaporated to dryness to afford example 2 (2S)-N-[5-[[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-methoxy-2-phenyl-acetamide (95 mg, 27.8%) as a white solid. 1H NMR (400 MHz, MeOD, 22° C.) δ 2.16-2.23 (m, 1H), 2.36-2.44 (m, 1H), 3.44 (s, 3H), 3.55-3.69 (m, 3H), 3.82-3.86 (m, 1H), 4.46-4.51 (m, 1H), 4.93 (s, 1H), 7.15-7.19 (m, 1H), 7.24-7.27 (m, 1H), 7.35-7.43 (m, 3H), 7.47-7.49 (m, 2H). m/z: ES+ [M+H]+ 430.
  • 71
  • [ 26164-26-1 ]
  • N2-[(3R)-1-(5-chloropyridazin-3-yl)pyrrolidin-3-yl]-1,3,4-thiadiazole-2,5-diamine [ No CAS ]
  • (2S)-N-[5-[[(3R)-1-(5-chloropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-methoxy-2-phenylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 25℃; for 18h; Inert atmosphere; 12 Example 12 DIPEA (0.04 mL, 0.20 mmol), N2-[(3R)-1-(5-chloropyridazin-3-yl)pyrrolidin-3-yl]-1,3,4-thiadiazole-2,5-diamine (Intermediate 9, 40 mg, 0.13 mmol) and (2S)-2-methoxy-2-phenylacetic acid (20 mg, 0.13 mmol) were added to a solution of HATU (61 mg, 0.16 mmol) in DMF (2 mL). The mixture was stirred at 25° C. for 18 hrs. This was then diluted with water (5 mL) and then extracted into DCM (10 mL) and evaporated under reduced pressure. The crude product was purified by preparative HPLC (SunFire C18 column, 5 μm, 50 mm×19 mm at 25 mL/min). Decreasingly polar ratios of water and MeCN containing 0.1% formic acid were used as a mobile phase. Appropriate fractions were then evaporated and re-purified by basic preparative chromatography. An)(Bridge column (5 micron, C18, 50×19 mm) was used. Decreasingly polar ratios of water water containing 0.1% ammonium hydroxide and acetonitrile were used as the mobile phase. The pure fractions were then evaporated and dried in the vacuum oven to afford: (0178) (2S)-N-[5-[[(3R)-1-(5-chloropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-methoxy-2-phenyl-acetamide as a white solid (15 mg, 25%). 1H NMR (400 MHz, DMSO-d6, 25° C.) δ 1.98 2.14 (1H, m), 2.17-2.36 (1H, m), 3.30 (3H, s), 3.44-3.64 (3H, m), 3.69-3.81 (1H, m), 4.28-4.42 (1H, m), 4.96 (1H, s), 7.11 (1H, d), 7.30-7.47 (5H, m), 7.69 (1H, d), 8.55 (1H, d), 12.24 (1H, s). m/z: ES+ [M+H]+ 446, 448
  • 72
  • [ 26164-26-1 ]
  • N2-[(3R)-1-(5-methylpyridazin-3-yl)pyrrolidin-3-yl]-1,3,4-thiadiazole-2,5-diamine [ No CAS ]
  • (2S)-2-methoxy-N-[5-[[(3R)-1-(5-methylpyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-phenylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
18% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 17 - 30℃; for 2h; Inert atmosphere; 13 Example 13 DIPEA (0.09 mL, 0.54 mmol), HATU (164 mg, 0.43 mmol) and (2S)-2-methoxy-2-phenylacetic acid (60 mg, 0.36 mmol) were added to a solution of N2-[(3R)-1-(5-methylpyridazin-3-yl)pyrrolidin-3-yl]-1,3,4-thiadiazole-2,5-diamine (Intermediate 7, 100 mg, 0.36 mmol) in DMF (2 mL). The mixture was stirred at room temperature for 2 hrs. This was then diluted with water (5 mL), extracted into DCM (10 mL) and evaporated under reduced pressure. The crude product was purified by preparative HPLC (SunFire C18 column, 5 μm, 50 mm×19 mm at 25 mL/min). Decreasingly polar ratios of water and MeCN containing 0.1% formic acid were used as a mobile phase. The fractions collected were then passed down an SCX cartridge washing with methanol before eluting with 2M ammonia in methanol. The ammonia in methanol was evaporated and the residue was dried in a vacuum oven to afford: (0181) (2S)-2-methoxy-N-[5-[[(3R)-1-(5-methylpyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-phenyl-acetamide as a white solid (28 mg, 18%). 1H NMR (400 MHz, DMSO-d6, 25° C.) δ 2.01 2.10 (1H, m), 2.19 (3H, s), 2.22-2.34 (1H, m), 3.31 (3H, s), 3.42-3.60 (3H, m), 3.70-3.74 (1H, m), 4.30-4.42 (1H, m), 4.98 (1H, s), 6.70 (1H, s), 7.30-7.42 (3H, m), 7.43-7.49 (2H, m), 7.70 (1H, d), 8.35 (1H, s), 12.26 (1H, s). m/z: ES+ [M+H]+ 426
  • 73
  • [ 1093192-07-4 ]
  • [ 26164-26-1 ]
  • C20H30N2O6 [ No CAS ]
  • 74
  • [ 26164-26-1 ]
  • (1S)-1-cyclopropylethan-1-amine [ No CAS ]
  • (S)-N-((S)-1-cyclopropylethyl)-2-methoxy-2-phenylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In ethyl acetate; acetonitrile at 20℃; 4 (S)-N-((S)-1-Cyclopropylethyl)-2-methoxy-2-phenylacetamide 2a To a suspension of (S)-2-methoxy-2-phenylacetic acid (100 mg, 0.60 mmol) in acetonitrile (1 mL) and ethyl acetate (1 mL) at rt were added (S)-1-cyclopropylethan-1-amine (74 mg, 0.87 mmol), DIPEA (0.315 mL, 1.81 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (T3P), 50% solution in EtOAc (0.72 mL, 1.20 mmol), the resulting clear solution was stirred at rt overnight. Solvents were evaporated, the residue was partitioned between EtOAc (5 mL) and water (2 mL), and the organic phase was washed with water (2 mL), NaHCO3 (aq) (2 mL) and brine. The EtOAc phase was filtered through a 1 g silica column that was washed with additional EtOAc to elute a product. The filtrate was concentrated, diluted with heptane and evaporated to dryness to afford compound 2a as a colourless solid (133 mg, 95%). [α]20D = +78 (c 1, MeCN). 1H NMR (500 MHz, CDCl3) δ 0.22-0.28 (m, 1H), 0.36-0.42 (m, 1H), 0.45-0.56 (m, 2H), 0.83-0.91 (m, 1H), 1.18 (d, J = 6.6 Hz, 3H), 3.34-3.42 (m, 1H), 3.38 (s, 3H), 4.59 (s, 1H), 6.72 (d, J = 5.9 Hz, 1H), 7.28-7.41 (m, 5H). 13C NMR (126 MHz, CDCl3) δ 3.25, 3.40, 17.49, 20.47, 49.42, 57.32, 83.96, 127.12 (2C), 128.47, 128.65 (2 C), 137.39, 169.78. LCMS (ESI) m/z calculated for C14H19NO2 (M+H)+ 234.2 found 234.2, tR=1.69 min, purity 99%.
  • 75
  • [ 6240-96-6 ]
  • [ 26164-26-1 ]
  • (S)-N-((R)-1-cyclopropylethyl)-2-methoxy-2-phenylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In ethyl acetate; acetonitrile at 20℃; 5 (S)-N-((S)-1-Cyclopropylethyl)-2-methoxy-2-phenylacetamide 2a General procedure: To a suspension of (S)-2-methoxy-2-phenylacetic acid (100mg, 0.60mmol) in acetonitrile (1mL) and ethyl acetate (1mL) at rt were added (S)-1-cyclopropylethan-1-amine (74mg, 0.87mmol), DIPEA (0.315mL, 1.81mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (T3P), 50% solution in EtOAc (0.72mL, 1.20mmol), the resulting clear solution was stirred at rt overnight. Solvents were evaporated, the residue was partitioned between EtOAc (5mL) and water (2mL), and the organic phase was washed with water (2mL), NaHCO3 (aq) (2mL) and brine. The EtOAc phase was filtered through a 1g silica column that was washed with additional EtOAc to elute a product. The filtrate was concentrated, diluted with heptane and evaporated to dryness to afford compound 2a as a colourless solid (133mg, 95%). 4.5 (S)-N-((R)-1-Cyclopropylethyl)-2-methoxy-2-phenylacetamide 2b Prepared as described for compound 2a but starting from (S)-2-methoxy-2-phenylacetic acid (100 mg, 0.60 mmol) and (R)-1-cyclopropylethan-1-amine (75 mg, 0.88 mmol) to afford compound 2b as a colourless solid (126 mg, 90%). [α]20D = +64 (c 1, MeCN). 1H NMR (500 MHz, CDCl3) δ 0.13-0.2 (m, 1H), 0.21-0.27 (m, 1H), 0.35-0.42 (m, 1H), 0.43-0.5 (m, 1H), 0.8-0.88 (m, 1H), 1.26 (d, J = 6.6 Hz, 3H), 3.36 (s, 3H), 3.38-3.47 (m, 1H), 4.57 (s, 1H), 6.71 (brd, J = 6.7 Hz, 1H), 7.29-7.42 (m, 5H). 13C NMR (126 MHz, CDCl3) δ 2.88, 3.13, 17.44, 20.59, 49.00, 57.22, 84.05, 127.25 (2 C), 128.53, 128.66 (2 C), 137.43, 169.78. LCMS (ESI) m/z calculated for C14H19NO2 (M+H)+ 234.2 found 234.2, tR=1.69 min, purity 99%.
  • 76
  • [ 26164-26-1 ]
  • ethyl 6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-5,6-dihydro pyrrolo[3,4-c]pyrazole-2(4H)-carboxylate [ No CAS ]
  • (S)-N-[5-(2-methoxy-2-phenylacetyl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl]-1-(trimethylsilyl)cyclobutane carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% Stage #1: (S)-2-methoxy-2-phenylacetic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0℃; for 3h; Inert atmosphere; Stage #2: ethyl 6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-5,6-dihydro pyrrolo[3,4-c]pyrazole-2(4H)-carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 15h; Inert atmosphere; Stage #3: With N,N-dimethylethylenediamine In dichloromethane at 20℃; for 3h; Inert atmosphere; 89 (S)-N-[5-(2-Methoxy-2-phenylacetyl)-6,6-dimethyl-1,4,5,6-tetrahydrop yrrolo[3,4-c]pyrazol-3-yl]-1-(trimethylsilyl)cyclobutanecarboxamide (compound No. IV-1176) To a solution of 263 mg (1.58 mmol) of (S)-2-methoxy-2-phenylacetic acid in 5 ml of dehydrated dichloromethane, 0.24 ml (2.8 mmol) of oxalyl chloride and 0.025 ml (0.32 mmol) of DMF were added in this order at 0°C in an argon atmosphere and then stirred for 3 hours with the temperature unchanged. After the completion of the reaction, the reaction solution was concentrated under reduced pressure at room temperature to obtain a concentration residue. To a solution of 300 mg (0.793 mmol) of ethyl 6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-5,6-dihydro pyrrolo[3,4-c]pyrazole-2(4H)-carboxylate synthesized in the similar manner as in Reference Example 84 and 0.55 ml (3.2 mmol) of DIPEA in 5 ml of dehydrated dichloromethane, a solution of the obtained concentration residue in 3 ml of dehydrated dichloromethane was added dropwise at 0°C in an argon atmosphere and then stirred at room temperature for 15 hours. Subsequently, 0.37 ml (4.0 mmol) of N,N-dimethylethane-1,2-diamine was added to the reaction solution at room temperature and then stirred for 3 hours with the temperature unchanged. After the completion of the reaction, a saturated aqueous solution of sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. All of the obtained organic layers were washed with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium chloride in this order, dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was subjected to silica gel column chromatography (DIOL silica gel, elution solvent: n-hexane:ethyl acetate = 50:50 to 35:65 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure. The obtained concentration residue was dissolved by adding ethyl acetate, then n-hexane was added, and the deposited solid was collected by filtration and dried under reduced pressure to obtain 206 mg of the title compound (yield: 57%) as a white solid. Mass spectrum (CI, m/z): 455 [M+1]+. 1H-NMR spectrum (400 MHz, DMSO-d6) δ: 12.26 & 11.86 (br s, total 1H), 9.71 - 9.45 (m, 1H), 7.46 - 7.26 (m, 5H), 4.96 (s, 1H), 4.73 - 4.53 (m, 1H), 4.30 (br d, J = 12.3 Hz, 1H), 3.31 (s, 3H), 2.47 - 2.36 (m, 2H), 2.24 - 2.11 (m, 2H), 1.89 - 1.53 (m, 8H), 0.05 (s, 9H).
  • 77
  • [ 26164-26-1 ]
  • C13H24O5 [ No CAS ]
  • C22H32O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h; Compound 8 To a solution of compound 7a (15 mg, 0.058 mmol) in dry DCM (1.5 mL) was added EDCI (18 mg, 0.09 mmol), DMAP (3.5 mg, 0.03 mmol) and (S)-(+)- Methoxyphenylaceticacid (12 mg, 0.075 mmol), this mixture was stirred for 3h at room temperature, the mixture was quenched with water, then extracted into DCM (3 x 10 mL). The combined organic layer was dried over Na2SO4 and concentrated to give crude residue which was purified over silica gel column chromatography (PE /EA = 8:1) to afford pure compound 8 (18 mg, 74% yield) as white solid. [a]24D = +100.6 (c = 0.30, CHCl3); IR (neat) νmax: 3438, 2926, 1749, 1619, 1455, 1377, 1112, 1064, 848cm-1. 1H NMR (400 MHz, CDCl3) δ 7.49 - 7.42 (m, 2H), 7.38 - 7.29 (m, 3H), 5.12 (m, 1H), 4.74 (s, 1H), 4.02 (dd, J = 8.6, 6.2 Hz, 1H), 3.83 (dd, J = 8.6, 5.4 Hz, 1H), 3.70 (dt, J = 9.7, 6.1 Hz, 1H), 3.41 (s, 3H), 3.36 - 3.29 (m, 2H), 1.94 (ddd, J = 14.5, 9.9, 1.7 Hz, 1H), 1.54 (m, 1H), 1.36 (d, J = 4.3 Hz, 6H), 1.30 (d, J = 6.3 Hz, 3H), 1.26 (s, 3H), 1.04 (s, 3H).13C NMR (100 MHz, CDCl3) δ 170.1, 136.8, 128.6, 127.3, 109.5, 108.9, 82.5, 81.0, 76.9, 76.3, 69.5, 67.7, 57.3, 39.7, 29.8, 27.2, 26.7, 26.5, 25.4, 20.8. HRMS (ESI-TOF): m/z [M+H]+C22H33O7: 409.2226, found: 409.2223.
  • 78
  • [ 26164-26-1 ]
  • 1-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)ethanol [ No CAS ]
  • (2S)-(R)-1-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
19.71% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; 25.4 Step-4: Synthesis of (2S)-1-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenyl acetate To a stirred solution of 1-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)ethanol (0.22 g, 0.913 mmol) and (S)-2-methoxy-2-phenylacetic acid (0.167 g, 1.005 mmol) in DCM (30 mL) was added DCC (0.226 g, 1.096 mmol), DMAP (0.030 g, 0.246 mmol) and stirred at room temperature for 16 h. Reaction was monitored by TLC. On completion, D.M. water (50 mL) was added to reaction mixture and extracted with DCM (2×50 mL). Organic layers were combined, washed with brine solution (50 mL), dried over sodium sulphate and concentrated under reduced pressure to give crude product. Crude product was purified by column chromatography using (silica gel, 100-200 mesh, 0-20% EtOAc in hexane as eluent) to give 1-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenylacetate (0.320 g) mixture which was separated by Prep HPLC to give (2S)-(R)-1-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenylacetate (0.035 g, 19.71%) as off white solid. (0519) MS: 390.15 [M++1]
  • 79
  • [ 26164-26-1 ]
  • 1-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethanol [ No CAS ]
  • (2S)-(R)-1-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
26.59% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; 16.4 Step-4: Synthesis of (2S)-(R)-1-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenylacetate Step-4: Synthesis of (2S)-(R)-1-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenylacetate To a stirred solution of 1-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethanol (0.080 g, 0.290 mmol) and (S)-2-methoxy-2-phenylacetic acid (0.048 g, 0.319 mmol) in DCM (10 mL) was added DCC (0.089 g, 0.435 mmol), DMAP (0.014 g, 0.116 mmol) and stirred at room temperature for 16 h. Reaction was monitored by TLC. On completion, D.M. water was added to reaction mixture and extracted with DCM. Organic layers were combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to give crude product. Crude product was purified by column chromatography using (silica gel, 100-200 mesh, 0-8% EtOAc in hexane as eluent) to give (0.120 g) mixture which was separated by Prep HPLC to give (2S)-(R)-1-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethyl 2-methoxy-2-phenylacetate (0.016 g, 26.59%) as colourless gum. MS: 424.2 [M++1]
  • 80
  • [ 26164-26-1 ]
  • (S)-(+)-1-(2,3-dimethyl-1H-indol-1-yl)propan-2-ol [ No CAS ]
  • C22H25NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3h; Esterification of (S)-(+)-1-(2,3-dimethyl-1H-indol-1-yl)propan-2-ol (S)-(+)-3c with (R)- or (S)-α-methoxy-α-phenylacetic acid General procedure: A solution of enantiopure indole-like alcohol (S)-(+)-3c (13.3mg, 0.07mmol, >99% ee), (R)- or (S)-α-methoxy-α-phenylacetic acid (10.9mg, 0.07mmol) as appropriate, DCC (16.2mg, 0.07mmol) and DMAP (15mg) in anhydrous CH2Cl2 (4mL) was stirred for 3h at room temperature. Next, the precipitated dicyclohexylurea (DCU) was removed by filtration, and the urea cake was rinsed with CH2Cl2 (10mL). The combined CH2Cl2 solutions were washed with saturated NaHCO3 (3×10mL) and H2O (10mL), dried over anhydrous MgSO4, and after filtration of the drying agent evaporated in vacuum. The crude product was purified by preparative layer chromatography using a mixture of 50% EtOAc/n-hexane as an eluent to afford the corresponding products 6 or 7 as yellowish oils. Yield=82%; 1H NMR (500MHz, CDCl3) δ: 1.26 (d, J=6.4Hz, 3H), 2.18 (s, 3H), 2.23 (s, 3H), 3.31 (s, 3H), 3.95 (dd, J=15.2, 5.9Hz, 1H), 4.14 (dd, J=15.2, 7.3Hz, 1H), 4.67 (s, 1H), 5.20-5.30 (m, 1H), 7.04-7.17 (m, 2H), 7.22-7.48 (m, 7H)
  • 81
  • [ 26164-26-1 ]
  • (2R,3R)-1-[(4-methoxybenzyl)oxy]-3-methylpent-4-en-2-ol [ No CAS ]
  • (2R,3R)-1-((4-methoxybenzyl)oxy)-3-methylpent-4-en-2-yl (S)-2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With dmap; dicyclohexyl-carbodiimide In dichloromethane for 0.75h; 4.4 4.4 (2R,3R)-1-((4-Methoxybenzyl)oxy)-3-methylpent-4-en-2-yl(S)-2-methoxy-2-phenylacetate I To a solution of the alcohol 5 (11.8 mg, 0.05 mmol) in anhydrous CH2Cl2 (2 mL) were added (S)-O-methyl mandelic acid (8.3 mg, 0.05 mmol), DCC (12 mg, 0.06 mmol) and a few crystals of DMAP and the mixture was stirred for 45min. The solvent was removed under vacuum and the residue was purified by flash column chromatography on silica gel using 10-15% EtOAc/hexane (v/v) as the eluent to afford ester I (16.2 mg, 0.042 mmol) in 84% yield as a colourless oil. 1H NMR (400MHz, CDCl3): δ 7.46-7.41 (m, 2H), 7.36-7.28 (m, 3H), 7.22 (d, J=8.7Hz, 2H), 6.87 (d, J=8.7Hz, 2H), 5.44 (ddd, J=18.5, 10.4, 8.2Hz, 1H), 5.06-5.01 (m, 1H), 4.86-4.79 (m, 2H), 4.75 (s, 1H), 4.46 (d, J=11.5Hz, 1H), 4.38 (d, J=11.5Hz, 1H), 3.81 (s, 3H), 3.51 (dd, J=10.8, 6.2Hz, 1H), 3.47 (dd, J=10.8, 4.5Hz, 1H), 3.40 (s, 3H), 2.47-2.36 (m, 1H), 0.71 (d, J=7.0Hz, 3H)
  • 82
  • [ 26164-26-1 ]
  • [ 109462-44-4 ]
  • C16H20O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dicyclohexyl-carbodiimide In dichloromethane at 0℃; 3.4.1. General Method for the Synthesis of MPA Esters of Secondary Alcohols General procedure: To a solution of the corresponding secondary alcohol (0.1 mmol) in dry CH2Cl2 were added1.1 equivalent of N,N’-dicyclohexylcarbodiimide (DCC) (0.11 mmol, 23 mg) and 1.1 equivalent of thecorresponding (R) or (S) MPA (0.11 mmol, 18 mg) and the reaction mixture was stirred at 0 °C for4-6 h. After completion of the reaction, the produced urea was filtered and the filtrate was evaporatedand then purified by column chromatography with 5/1 Hex/EtOAc. The produced correspondingMPA-ester was isolated with 90% isolated yield.
  • 83
  • [ 26164-26-1 ]
  • 6-ethoxy-4-(6-(piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile dihydrochloride [ No CAS ]
  • [ 76-05-1 ]
  • C28H28N6O3*C2HF3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
32.5% Stage #1: (S)-2-methoxy-2-phenylacetic acid; 6-ethoxy-4-(6-(piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile dihydrochloride With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h; Stage #2: trifluoroacetic acid In water; acetonitrile 37 (S)-6-ethoxy-4-(6-(4-(2-methoxy-2-phenylacetyl)piperazin- 1 -yl)pyridin-3 - yl)pyrazolo[ 1.5 -alpyridine-3 -carbonitrile 2.2.2-trifluoroacetate A solution of 6-ethoxy-4-(6-(piperazin- 1 -yl)pyridin-3 -yl)pyrazolo[ 1,5 -a]pyridine3-carbonitrile dihydrochloride (Example 30; 30 mg, 0.0861 mmol) in DCM (1.72 mL) was treated with (S)-2-methoxy-2-phenylacetic acid (17.2 mg, 0.103 mmol), HATU (39.3 mg, 0.103 mmol) and DIEA (60.0 tL, 0.344 mmol). The resulting mixture was stirred 16 h at ambient temperature and then concentrated in vacuo. The residue was purified by Cl 8 reverse phase chromatography (5-95% ACN in water with 0.1% TFA as the gradient eluent) to cleanly provide the title compound (13.9 mg, 32.5% yield). MS (apci) m/z = 497.2 (M+H).
  • 84
  • [ 26164-26-1 ]
  • C12H21NO6 [ No CAS ]
  • methyl 3-((4R)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-3-((S)-2-methoxy-2-phenylacetamido)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% Stage #1: (S)-2-methoxy-2-phenylacetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.25h; Inert atmosphere; Stage #2: C12H21NO6 With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere; (S)-methyl3-((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]diox ol-4-yl)-3-((S)-2-methoxy-2-phenylacetamido)propanoate (5C) A solution of (S)-Mosher acid (0.03 g, 0.20 mmol), HOBt (0.04 g, 0.27 mmol) and EDCI (0.05 g, 0.27 mmol) in CH2Cl2 (5 mL) was stirred at 0 °C under a N2 atmosphere for 15 min. It was sequentially treated with amine 5a (0.07 g, 0.18 mmol) in dry CH2Cl2 (0.5 mL) at 0 °C was treated with CF3COOH (0.1 mL) and DIPEA (0.1 mL, 0.55 mmol) and stirred for an additional 5 h. Work up as described for 1 and purified the residue by column chromatography (60-120 mesh Silica gel, 50% ethyl acetate in pet. ether) to afford 5c (0.04 g, 61%) as a white solid; mp 111-114 °C; [a]28D + 198.1 (c 0.18, CHCl3); IR (KBr): 3367, 2926, 1740, 1672, 1534, 1201, 1084, 1020 cm-1; 1H NMR (400 MHz, CDCl3, 303 K): d 7.40-7.30 (m, 5H, Ar-H), 7.04 (d, 1H, J = 9.8 Hz, NH), 5.77 (d, 1H, J = 3.5 Hz, C1H), 4.68 (s, 1H, C2H), 4.63-4.58 (m, 2H, Cα'H, CβH), 4.08 (dd, 1H, J = 9.0, 1.8 Hz, C3H), 3.50 (s, 3H, COOMe), 3.44 (s, 3H, OMe), 3.38 (dd, 1H, J = 9.0, 4.3 Hz, C4H), 3.35 (s, 3H, SuOMe), 2.58 (m, 2H, CαH), 1.58 (s, 3H, Me), 1.37 (s, 3H, Me); HRMS (ESI+): m/z calculated for C21H29NO8 [M++Na] 446.1790, found 446.1799.
  • 85
  • [ 26164-26-1 ]
  • C14H22O [ No CAS ]
  • (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-2-yl (S)-2-methoxy-2-phenylacetate [ No CAS ]
  • (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-yl (S)-2-methoxy-2-phenylacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; 6A.5 Step 5: Preparation of (2R,35) and (25,3R)-3-(2, 5-dimethylphenyl)-4-methylpentan-2-yl (S)-2-methoxy-2- phenylacetate. To a racemic mixture containing (2R,35) and (2S, 3R)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol (0.491 g,2.380 mmol) dissolved in 16 mE of CH2C12 was added N,N-dimethylpyridin-4-amine (0.029 g, 0.238 mmol) and (S)-2-methoxy-2-phenylacetic acid (0.514 g, 3.09 mmol). The reaction was cooled to 0° C. followed by addition of 3-(((ethylimino)methylene)amino)-N,N-dimethylpropan-1 - amine hydrochloride (0.9 12 g, 4.76 mmol) was added and the reaction was warmed to room temperature and stirred overnight. The mixture was concentrated under reduced pressure. The residue was purified by automated silica gel chromatography (Isco, 80 g 5i02 column, 0-10% MTI3E in hexanes as the eluent) to provide (2R,35)-3-(2,5-dimethyl- phenyl)-4-methylpentan-2-yl (S)-2-methoxy-2-phenylac- etate (284.7 mg 32%) and (25,3R)-3-(2,5-dimethylphenyl)- 4-methylpentan-2-yl (S)-2-methoxy-2-phenylacetate as colorless oils. Only the desired (2R,35) diastereomer was characterized. ‘H NMR (500 MHz, CDC13) ö 7.44-7.37 (m, 2H), 7.36-7.27 (m, 3H), 7.18 (s, 1H), 7.00 (d, J=7.7 Hz, 1H),6.93-6.80 (m, 1H), 5.42-5.34 (m, 1H), 4.74 (s, 1H), 3.40 (s, 3H), 2.62 (dd, J=9.7, 4.3 Hz, 1H), 2.30 (s, 3H), 2.21 (s, 3H),2.05-1.92 (m, 1H), 0.93 (d, J=6.5 Hz, 3H), 0.87 (d, J=6.3 Hz, 3H), 0.68 (d, J=6.7 Hz, 3H). ‘3C NMR (126 MHz, CDC13) ö 170.32, 139.03, 136.46, 134.96, 133.92, 129.67, 128.80, 128.51, 126.90, 126.67, 82.86, 72.23, 57.31, 51.06, 30.54,21.31, 21.00, 20.93, 20.23, 17.82. HRMS-ESI (m/z) [M+Na]+ calcd for C23H3Q03, 377.2087; found, 377.2089.
  • 86
  • [ 26164-26-1 ]
  • (3R)-1-[3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl]pyrrolidin-3-amine hydrochloride [ No CAS ]
  • (2S)-N-[(3R)-1-[3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl]pyrrolidin-3-yl]-2-methoxy-2-phenylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide for 14h; 36 (^-N (i?)-l-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[l,2- )]pyridazin-8- yl)pyrrolidin-3-yl)-2-methoxy-2-phenylacetamide (36 a solution of la (160 mg, 0.4 mmol), DIPEA (0.3 mL, 2 mmol) and (5 -2-methoxy-2-phenylacetic acid (100 mg, 0.6 mmol) in DMF (5 mL) was added HATU (182.5 mg, 0.48 mmol) and reaction mixture was stirred for 14 h and then solvent was evaporated. Residue was chromatographed on silica gel column (75 g, toluene: acetone 3: 1) to afford product (154 mg, 75%) as foam, fif = +97.5 (c 0.279, (0543) CHC13). H NMR (400 MHz, d6-DMSO) δ 1.93 - 2.04 (m, 1H), 2.11 - 2.22 (m, 1H), 2.29 (s, 3H), 2.39 (s, 3H), 3.28 (s, 3H), 3.78 (s) and 3.81 (s) and 3.82 (br s, 9H), 4.07 (br s, 1H), 4.36 - 4.46 (m, 1H), 4.66 (s, 1H), 5.80 (s, 1H), 7.07 (d, J= 8.4 Hz, 1H), 7.17 (dd, J = 8.3, 2.0 Hz, 1H), 7.47 - 7.25 (m, 6H), 8.44 (d, J= 7.1 Hz, 1H). 1 C NMR (101 MHz, d6-DMSO) δ 15.0, 21.7, 30.5, 48.6, 54.5, 55.7, 56.9, 83.3, 94.0, 111.8, 113.2, 122.0, 122.2, 123.9, 127.2, 128.2, 128.4, 131.9, 136.6, 138.1, 141.2, 148.3, 148.4, 151.4, 170.1. HRMS calcd for C29H34N5O4 m/z: 516.2605 (M+H)+, found 516.2562
  • 87
  • [ 26164-26-1 ]
  • [ 225110-25-8 ]
  • C35H40O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h; S1.4.10. Synthesis of MPA esters of ()-notopolyenol A ((±)-1) and falcarindiol (5) General procedure: MPA esters were prepared according to the method reported by Yang Zhao et al. [18] with a slight modification. To a solution of the alcohol compound (1.5 mg) in dry DCM (0.5 mL) was added R or S-MPA (2 mg, 0.012 mmol, 2.0 equiv), DCC (2.4 mg, 0.012 mmol, 2.0 equiv) and catalytic amount of DMAP. After reacting at room temperature for 2 h, the crude product was purified by preparative TLC eluting with PE/EtOAc to afford the corresponding MPA ester.
  • 88
  • [ 26164-26-1 ]
  • truncateol O [ No CAS ]
  • (S)-MPA ester of truncateol O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In chloroform-d1 at 20℃; for 24h; 3.5. Preparation of (R)- and (S)-MPA esters General procedure: To a CDCl3 solution (0.3 mL) containing 1 (0.83 mg, 0.003 mmol) were added (R)-MPA (2.0 mg, 0.012 mmol), DMAP (0.8 mg, 0.006 mmol), and N, N-dicyclohexylcarbodiimide (DCC, 2.5 mg, 0.012 mmol). After reacting at rt for 24 h, the crude products were separated by silica gel column chromatography eluting with petroleum ether/acetone (4:1) to afford the (R)-MPA ester. By the same protocol, the (S)-MPA ester was prepared from (S)-MPA. Following the same protocol as that for 1, the (R)-MPA ester and the (S)-MPA ester were obtained from 2-5.
  • 89
  • [ 26164-26-1 ]
  • truncateol P [ No CAS ]
  • (S)-MPA ester of truncateol P [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In chloroform-d1 at 20℃; for 24h; 3.5. Preparation of (R)- and (S)-MPA esters General procedure: To a CDCl3 solution (0.3 mL) containing 1 (0.83 mg, 0.003 mmol) were added (R)-MPA (2.0 mg, 0.012 mmol), DMAP (0.8 mg, 0.006 mmol), and N, N-dicyclohexylcarbodiimide (DCC, 2.5 mg, 0.012 mmol). After reacting at rt for 24 h, the crude products were separated by silica gel column chromatography eluting with petroleum ether/acetone (4:1) to afford the (R)-MPA ester. By the same protocol, the (S)-MPA ester was prepared from (S)-MPA. Following the same protocol as that for 1, the (R)-MPA ester and the (S)-MPA ester were obtained from 2-5.
  • 90
  • [ 26164-26-1 ]
  • truncateol Q [ No CAS ]
  • (S)-MPA ester of truncateol Q [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In chloroform-d1 at 20℃; for 24h; 3.5. Preparation of (R)- and (S)-MPA esters General procedure: To a CDCl3 solution (0.3 mL) containing 1 (0.83 mg, 0.003 mmol) were added (R)-MPA (2.0 mg, 0.012 mmol), DMAP (0.8 mg, 0.006 mmol), and N, N-dicyclohexylcarbodiimide (DCC, 2.5 mg, 0.012 mmol). After reacting at rt for 24 h, the crude products were separated by silica gel column chromatography eluting with petroleum ether/acetone (4:1) to afford the (R)-MPA ester. By the same protocol, the (S)-MPA ester was prepared from (S)-MPA. Following the same protocol as that for 1, the (R)-MPA ester and the (S)-MPA ester were obtained from 2-5.
  • 91
  • [ 26164-26-1 ]
  • truncateol R [ No CAS ]
  • (S)-MPA ester of truncateol R [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In chloroform-d1 at 20℃; for 24h; 3.5. Preparation of (R)- and (S)-MPA esters General procedure: To a CDCl3 solution (0.3 mL) containing 1 (0.83 mg, 0.003 mmol) were added (R)-MPA (2.0 mg, 0.012 mmol), DMAP (0.8 mg, 0.006 mmol), and N, N-dicyclohexylcarbodiimide (DCC, 2.5 mg, 0.012 mmol). After reacting at rt for 24 h, the crude products were separated by silica gel column chromatography eluting with petroleum ether/acetone (4:1) to afford the (R)-MPA ester. By the same protocol, the (S)-MPA ester was prepared from (S)-MPA. Following the same protocol as that for 1, the (R)-MPA ester and the (S)-MPA ester were obtained from 2-5.
  • 92
  • [ 26164-26-1 ]
  • truncateol S [ No CAS ]
  • (S)-MPA ester of truncateol S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In chloroform-d1 at 20℃; for 24h; 3.5. Preparation of (R)- and (S)-MPA esters General procedure: To a CDCl3 solution (0.3 mL) containing 1 (0.83 mg, 0.003 mmol) were added (R)-MPA (2.0 mg, 0.012 mmol), DMAP (0.8 mg, 0.006 mmol), and N, N-dicyclohexylcarbodiimide (DCC, 2.5 mg, 0.012 mmol). After reacting at rt for 24 h, the crude products were separated by silica gel column chromatography eluting with petroleum ether/acetone (4:1) to afford the (R)-MPA ester. By the same protocol, the (S)-MPA ester was prepared from (S)-MPA. Following the same protocol as that for 1, the (R)-MPA ester and the (S)-MPA ester were obtained from 2-5.
  • 93
  • [ 26164-26-1 ]
  • C9H17NO4*C2HF3O2 [ No CAS ]
  • C18H25NO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 8h; Inert atmosphere; 8.11 (R)-Methyl-3-((2R,3R)-3-methoxytetrahydrofuran-2-yl)-3-((S)-2-phenylpropanamido)propanoate (29) A solution of (S)-Mosher acid 25 (0.05g, 0.3mmol), HOBt (0.06g, 0.48mmol) and EDCI (0.09g, 0.48mmol) in CH2Cl2 (5mL) was stirred at 0°C under a N2 atmosphere for 15min, treated sequentially with 22a [prepared from 22 (0.1g, 0.3mmol) in dry CH2Cl2 (0.5mL) at 0°C treated with CF3COOH (0.1mL for 2h] and DIPEA (0.1mL, 0.6mmol) and stirred for 8h. Work up as described for 26 and purification of the residue by column chromatography (Silica gel 60-120 mesh, 80% EtOAc in pet. ether) afforded 29 (0.06g, 53%) as a pale yellow syrup; [α]D20=+1.4 (c 0.14, CHCl3); IR (CHCl3): 3396, 3062, 3030, 2926, 2830, 1729, 1666, 1520, 1261, 1094, 771, 698cm-1; 1H NMR (500MHz, CDCl3, 288K) δ 7.54 (d, 1H, J=9.4Hz, NH), 7.41 (m, 2H, Ar-H), 7.34 (m, 2H, Ar-H), 7.29 (m, 1H, Ar-H), 4.60 (s, 1H, Ar-CH), 4.60 (m, 1H, J=9.4, 6.7, 6.4, 5.4Hz, CβH), 3.90 (dd, 1H, J=6.7, 4.2Hz, C4H), 3.85 (q, 1H, J=8.6, Hz, C1H′), 3.79 (ddd, 1H, J=5.0, 4.2, 1.8Hz, C3H), 3.78 (dt, 1H, J=8.6, 4.0Hz, C1H), 3.68 (s, 3H, COOMe), 3.39 (s, 3H, OMe), 3.09 (s, 3H, OMe), 2.80 (dd, 1H, J=16.6, 6.4Hz, CαH′), 2.67 (dd, 1H, J=16.0, 5.4Hz, CαH), 2.01 (m, 1H, J=13.0, 8.6, 4.0, 1.8Hz, C2H′), 1.90 (dtd, 1H, J=13.0, 8.6, 4.0, 1.8Hz, C2H); 13C NMR (125MHz, CDCl3, 298K): δ 172.4, 170.0, 137.3, 128.3(2), 128.2, 126.8(2), 83.9, 81.6, 80.9, 66.5, 57.3, 56.6, 51.6, 45.6, 35.7, 31.0; HRMS (ESI+): m/z [M++H] calculated for C18H26O6N 352.1755, found 352.1750.
  • 94
  • [ 26164-26-1 ]
  • C9H17NO4*C2HF3O2 [ No CAS ]
  • C18H25NO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 8h; Inert atmosphere; 8.9 (S)-Methyl-3-((2R,3R)-3-methoxytetrahydrofuran-2-yl)-3-((S)-2-phenylpropanamido)prop anoate (27) A solution of (S)-Mosher acid 25 (0.04g, 0.2mmol), HOBt (0.04g, 0.34mmol) and EDCI (0.06g, 0.34mmol) in 17 CH2Cl2 (2mL) was stirred at 0°C under N2 atmosphere for 15min. It was treated sequentially with amine salt 1b and 41 DIPEA (0.1mL, 0.6mmol) and stirred at room temperature for an additional 8h. Work up as described for 26 and purification of the residue by column chromatography (Silica gel 60-120 mesh, 82% 12 EtOAc in 78 pet. ether) to afford 97 27 (0.05g, 68%) as a white solid; mp 94-96°C; [α]D20=+2.8 (c 0.17, CHCl3); IR (CHCl3): 3415, 3287, 3033, 2925, 2853, 1733, 1666, 1520, 1282, 1198, 1073, 772, 696cm-1; 1H NMR (400MHz, CDCl3, 288K) δ 7.42-7.29 (m, 5H, Ar-H), 7.25 (d, 1H, J=8.8Hz, NH), 4.59 (s, 1H, Ar-CH), 4.56 (m, 1H, J=8.8, 7.7, 6.2, 6.0Hz, CβH), 4.00 (q, 1H, J=8.3Hz, C1H′), 3.99 (dd, 1H, J=7.7, 5.0Hz, C4H), 3.94 (ddd, 1H, J=5.0, 5.0, 2.7Hz, C3H), 3.81 (dt, 1H, J=8.3, 5.2Hz, C1H), 3.53 (s, 3H, COOMe), 3.38 (s, 3H, OMe), 3.31 (s, 3H, OMe), 2.71 (dd, 1H, J=15.8, 6.2Hz, CαH′), 2.60 (dd, 1H, J=15.8, 6.0Hz, CαH), 2.05 (m, 1H, C2H′), 2.02 (m, 1H, C2H); 13C NMR (125MHz, CDCl3, 298K): δ 171.9, 170.0, 137.3, 128.4(2), 128.2, 127.0(2), 83.9, 81.2, 80.8, 66.6, 57.3, 56.9, 51.5, 45.8, 36.3, 31.3; HRMS (ESI+): m/z [M++H] calculated for C18H26O6N 352.1755, found 352.1750.
  • 95
  • [ 26164-26-1 ]
  • portimine A [ No CAS ]
  • C41H47NO9 [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.4 mg With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3h; 3.4. Preparation of MPA Esters 3 and 4 of Portimine General procedure: R)-α-methoxyphenylacetic acid (MPA, 12.4 mg), DMAP (1.5 mg), and DCC (10.1 mg) were added to a solution of portimine (0.5 mg) in dry CH2Cl2 (500 μL). The reaction mixture was stirred at room temperature for three hours. After completion of the reaction, the solvent was removed with N2 flow, and the residue was purified by normal phase thin layer chromatography (TLC) developed with n-hexane-EtOAc (5:3) to afford 0.4 mg of R-MPA ester (3). Similarly, 0.4 mg of S-MPA ester (4) was prepared.
  • 96
  • [ 26164-26-1 ]
  • (1E,5Z)-1,6-dichloro-2-methylhepta-1,5-dien-3-ol [ No CAS ]
  • C17H20Cl2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: (S)-2-methoxy-2-phenylacetic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.166667h; Inert atmosphere; Stage #2: (1E,5Z)-1,6-dichloro-2-methylhepta-1,5-dien-3-ol In dichloromethane at 0 - 20℃; for 48h; Inert atmosphere; 4.4. Preparation of MTPA esters 12a and 12b A solution of EDC.HCl (12 mg, 64 mol), S-(+)-α-methoxyphenylacetic acid (15 mg, 64 mol),and DMAP (14.8 mg, 120 mol) was stirred in dry CH2Cl2 (0.5 mL) under Ar at 0 °C for 10 min afterwhich 8 (4 mg, 12 mol) in CH2Cl2 (0.5 mL) was added. The solution was allowed to come to roomtemperature and stirred under Ar for 48 h. CH2Cl2 (10 mL) was added and the mixture was washedin turn with 10% HCl (10 mL), H2O (10 mL), sat. NaHCO3 (10 mL) and H2O (10 mL) before beingdried under reduced pressure. The sample was purified by flash silica gel chromatography (10:1hexanes:EtOAc) to yield the crude product 12a, analysed without further purification. The procedurewas repeated with R-(-)-α-methoxyphenylacetic acid to yield product 12b (see Figure S17-S20 in theSupplementary Materials). Compound 12a: 1H NMR (CDCl3, 600 MHz) δH 7.48-7.40 (5H, m, aromatics); 6.25 (1H, s, H-1); 5.50(1H, dd, H-3); 5.18 (1H, t, H-5); 3.51 (3H, s, OMe); 2.56 (2H, m, H-4); 2.03 (3H, s, H-7); 1.75 (3H, d, H-8).
  • 97
  • [ 26164-26-1 ]
  • C37H68O6Si2 [ No CAS ]
  • C46H76O8Si2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; Preparation of mandelate ester of alcohol 23 General procedure: To the solution of propargylic alcohol23(26 mg, 0.1 mmol) in DCM (1 mL)cooled at 0 C was added DCC (30 mg, 0.15 mmol), DMAP (1.2 mg), and (R)-methoxymandelic acid (20 mg, 0.12 mmol). The reaction mixture was stirred overnight while gradually allowing the temperature to rise to rt. The solvent was evaporated under reducedpressure to furnish the crude compound which was purified by column chromatography using 5% EtOAc/Hexanes (v/v) as the eluent to afford the ester in 95% yield as a liquid.
  • 98
  • [ 26164-26-1 ]
  • (rac)-5-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecan-2-one [ No CAS ]
  • 5-(4-fluorophenyl)-9-[(2S)-2-methoxy-2-phenylacetyl]-3,9-diazaspiro[5.5]undecan-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 12h; 32 (5R)-9-[2-(4-fluoro-2-methylphenyl)propanoyl]-5-phenyl-3,9-diazaspiro[5.5]undecan-2-one (mixture of stereoisomers) General procedure: N,N-diisopropylethylamine (460 mI, 2.6 mmol), (rac)-2-(4-fluoro-2-methylphenyl)propanoic acid (105 mg, 576 pmol; CAS No1248972-16-8) and HATU (299 mg, 786 pmol) were added to a solution of (5R)-5-phenyl-3,9-diazaspiro[5.5]undecan-2-one, salt with hydrochloric acid (147 mg, 524 mihoI, Intermediate 7) in DMF (6.3 ml) and the mixture was stirred for 12 h at room temperature. For the work-up, water was added, the mixture was extracted with ethyl acetate and the combined organic phases were dried and concentrated. The residue was purified by preparative HPLC (Method 6) to give the title compound 108 mg (48 % yield).LC-MS (Method 2): Rt= 1 .13 min; MS (ESIpos): m/z = 409 [M+H]+.1H-NMR (400 MHz, DMSO-d6) d [ppm] 0.229 (0.50), 0.241 (0 .50), 0.907 (1 .04), 0.920 (1 .00), 0.939 (0.92), 1 .090 (4.46), 1 .107 (4.85) 1 .123 (5.00), 1.140 (4.88), 1 .172 (0.54), 1.206 (0.92),1 .221 (0.92), 1 .257 (0.73), 1 .325 (1.00) 1 .988 (0.54), 1.998 (0.92), 2.012 (0.62), 2.040 (1 .04),2.073 (0.54), 2.104 (0.77), 2.139 (8.73) 2.220 (7.23), 2.268 (5.31 ), 2.276 (4.19), 2.323 (1 .65),2.327 (2.31 ), 2.331 (1 .65), 2.432 (1.15) 2.518 (9.81 ), 2.523 (6.27), 2.546 (1 .73), 2.589 (1 .23),2.665 (1 .77), 2.669 (2.42), 2.673 (1.85) 2.699 (0.92), 2.729 (1.42), 2.748 (0.73), 2.761 (1 .27),2.774 (0.92), 2.787 (0.96), 2.803 (0.65) 2.816 (0.77), 2.989 (0.69), 3.008 (0.58), 3.046 (0.88),3.076 (0.92), 3.105 (0.73), 3.159 (15.08), 3.172 (16.00), 3.188 (0.69), 3.344 (1 .85), 3.370 (1 .00), 3.404 (0.54), 3.485 (0.92), 3.513 (0.88), 3.877 (0.96), 3.893 (0.96), 3.946 (0.81 ), 3.963(0.88), 3.976 (0.65), 3.992 (0.81 ), 4.006 (0.62), 4.023 (0.62), 4.083 (1 .42), 4.096 (3.92), 4.109(3.88), 4.122 (1 .65), 4.280 (0.50), 6.368 (0.77), 6.374 (0.85), 6.639 (0.88), 6.654 (0.96), 6.661(0.88), 6.676 (0.81 ), 6.71 1 (0.65), 6.718 (0.73), 6.739 (0.50), 6.758 (0.88), 6.773 (0.96), 6.778 (0.58), 6.850 (0.81 ), 6.857 (0.85), 6.876 (0.85), 6.882 (0.81 ), 6.941 (1 .00), 6.950 (1.92), 6.959(2.38), 6.969 (2.00), 6.973 (1 .88), 6.989 (0.88), 7.015 (1.38), 7.041 (0.77), 7.048 (0.77), 7.062(1 .69), 7.079 (2.08), 7.250 (2.73), 7.266 (4.12), 7.272 (4.58), 7.284 (3.23), 7.309 (2.31 ), 7.328(1 .73), 7.348 (0.54), 7.607 (1.12), 7.627 (1 .31 ), 7.652 (1.31 ).
  • 99
  • [ 26164-26-1 ]
  • cytosporins F [ No CAS ]
  • C39H48O10 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h; 3.6. Preparation of (R)- and (S)-MPA Esters General procedure: Compound 7 (0.8 mg, 0.002 mmol), along with DMAP (0.5 mg, 0.004 mmol), N,N0-dicyclohexylcarbodiimide (0.8 mg, 0.004 mmol, DCC) and (R)-MPA (0.7 mg, 0.004 mmol), was mixed in anhydrous CH2Cl2 (0.3 mL). The solvent was removed after 2 h at room temperature. The (R)-MPA ester (7a) was obtained from the crude product by semipreparative HPLC (MeOH-H2O:0-2 min, 40%; 2-15 min; 15-25 min, 100%). Following a similar procedure, the (S)-MPA ester (7b) was obtained by using (S)-MPA. The above steps were also applied to compounds 17a, 18, 25, and 26.
  • 100
  • [ 26164-26-1 ]
  • cytosporin R [ No CAS ]
  • C55H62O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h; 3.6. Preparation of (R)- and (S)-MPA Esters General procedure: Compound 7 (0.8 mg, 0.002 mmol), along with DMAP (0.5 mg, 0.004 mmol), N,N0-dicyclohexylcarbodiimide (0.8 mg, 0.004 mmol, DCC) and (R)-MPA (0.7 mg, 0.004 mmol), was mixed in anhydrous CH2Cl2 (0.3 mL). The solvent was removed after 2 h at room temperature. The (R)-MPA ester (7a) was obtained from the crude product by semipreparative HPLC (MeOH-H2O:0-2 min, 40%; 2-15 min; 15-25 min, 100%). Following a similar procedure, the (S)-MPA ester (7b) was obtained by using (S)-MPA. The above steps were also applied to compounds 17a, 18, 25, and 26.
  • 101
  • [ 26164-26-1 ]
  • cytosporins K [ No CAS ]
  • C55H62O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h; 3.6. Preparation of (R)- and (S)-MPA Esters General procedure: Compound 7 (0.8 mg, 0.002 mmol), along with DMAP (0.5 mg, 0.004 mmol), N,N0-dicyclohexylcarbodiimide (0.8 mg, 0.004 mmol, DCC) and (R)-MPA (0.7 mg, 0.004 mmol), was mixed in anhydrous CH2Cl2 (0.3 mL). The solvent was removed after 2 h at room temperature. The (R)-MPA ester (7a) was obtained from the crude product by semipreparative HPLC (MeOH-H2O:0-2 min, 40%; 2-15 min; 15-25 min, 100%). Following a similar procedure, the (S)-MPA ester (7b) was obtained by using (S)-MPA. The above steps were also applied to compounds 17a, 18, 25, and 26.
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